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Information on EC 1.1.1.3 - homoserine dehydrogenase
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1.1.1.3 homoserine dehydrogenaseIUBMB Comments
The yeast enzyme acts most rapidly with NAD+; the Neurospora enzyme with NADP+. The enzyme from Escherichia coli is a multi-functional protein, which also catalyses the reaction of EC 2.7.2.4 (aspartate kinase).
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Word Map
- 1.1.1.3
- l-threonine
-
threonine-sensitive
- corynebacterium
- glutamicum
- l-lysine
- semialdehyde
- dihydrodipicolinate
- brevibacterium
- l-isoleucine
-
aspartate-derived
-
2.7.2.4
-
i-homoserine
-
rhodospirillum
- lactofermentum
-
lysine-sensitive
-
feedback-resistant
-
feedback-insensitive
- drug development
- synthesis
- agriculture
- pharmacology
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
AK-HDH, AK-HSD-1, AK-HSDH, AK-HseDH, aspartate kinase-homoserine dehydrogenase, aspartokinase-homoserine dehydrogenase I, bifunctional aspartate kinase-homoserine dehydrogenase, BsHSD, HDH, hom, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
AK-HSDH
AK-HseDH
aspartate kinase-homoserine dehydrogenase
bifunctional aspartate kinase-homoserine dehydrogenase
BsHSD
HDH
-
-
-
-
hom
hom-1
Hom6
homoserine dehydrogenase 1
homoserine dehydrogenase 2
HSD
HSDH
HseDH
orf19.2951
PbHSD
SACOL1362
StHSD
thrA
TM_0547
additional information
aspartate kinase-homoserine dehydrogenase
-
bifunctional enzyme EC 2.7.2.4/EC 1.1.1.3
HSD
-
-
-
-
HSDH
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
-
-
-
-
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
bifunctional enzyme showing aspartate kinase, 2.7.2.4, and homoserine dehydrogenase activities
-
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
bifunctional enzyme showing aspartate kinase, EC 2.7.2.4, and homoserine dehydrogenase activities
-
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
bifunctional enzyme showing aspartate kinase, EC 2.7.2.4, and homoserine dehydrogenase activities
-
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
bifunctional enzyme showing aspartate kinase, EC 2.7.2.4, and homoserine dehydrogenase activities
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
ordered bi bi kinetic mechanism in which nicotinamide cofactor binds first and leaves last in the reaction sequence
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
role of conserved water molecules and a lysine residue in hydride transfer between the substrate and the cofactor. Lys105, which is located at the interface of the catalytic and cofactor-binding sites, mediates the hydride transfer step of the reaction mechanism of the enzyme. Potential reaction mechanisms for homoserine dehydrogenase, overview
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
L-homoserine oxidation by StHSD proceeds through a sequentially ordered mechanism in which NAD+ binds to the free form of the enzyme, after which L-homoserine binds to the enzyme-NAD+ complex
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
proposed reaction mechanisms of hydride transfer from L-homoserine in the active site of Paracoccidioides brasiliensis homoserine dehydrogenase (HSD), Glu218 accepts a proton from the hydroxyl group of L-homoserine, which donates a hydride to the nC-4 carbon of NAD+. Lys233, Lys122, and the water molecule at position 374 (Wat374) serve to bind the substrate
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
two possible catalytic mechanisms of homoserine oxidation. (a) Lys99 is the acidx02base catalytic residue. The hydroxy group of L-Hse is activated by protonated Lys195, and a proton from the Od of L-Hse is captured by the deprotonated Lys99. Lys99 exists in the simple proton pathway, in which a proton can go in and out of an active site easily. (b) Lys195 is drown as an acidx02base catalytic residue. L-Hse and Asp191 exist deep inside of the active site and have no interaction to the surface. Thus, the direct proton pathway from Lys195 to the bulk water region cannot be realized. Lys99 and Lys195 of TtHSD are essential for catalysis
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
L-homoserine oxidation by StHSD proceeds through a sequentially ordered mechanism in which NAD+ binds to the free form of the enzyme, after which L-homoserine binds to the enzyme-NAD+ complex
-
-
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
proposed reaction mechanisms of hydride transfer from L-homoserine in the active site of Paracoccidioides brasiliensis homoserine dehydrogenase (HSD), Glu218 accepts a proton from the hydroxyl group of L-homoserine, which donates a hydride to the nC-4 carbon of NAD+. Lys233, Lys122, and the water molecule at position 374 (Wat374) serve to bind the substrate
-
-
L-homoserine + NAD(P)+ = L-aspartate 4-semialdehyde + NAD(P)H + H+
role of conserved water molecules and a lysine residue in hydride transfer between the substrate and the cofactor. Lys105, which is located at the interface of the catalytic and cofactor-binding sites, mediates the hydride transfer step of the reaction mechanism of the enzyme. Potential reaction mechanisms for homoserine dehydrogenase, overview
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-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
MetaCyc
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SYSTEMATIC NAME
IUBMB Comments
L-homoserine:NAD(P)+ oxidoreductase
The yeast enzyme acts most rapidly with NAD+; the Neurospora enzyme with NADP+. The enzyme from Escherichia coli is a multi-functional protein, which also catalyses the reaction of EC 2.7.2.4 (aspartate kinase).
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CAS REGISTRY NUMBER
COMMENTARY
9028-13-1
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-aspartate 4-semialdehyde + NADH
L-homoserine + NAD+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
kinetic mechanism
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
third reaction in the pathway between aspartate and the amino acids threonine, isoleucine, methionine
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
third reaction in the pathway between aspartate and the amino acids threonine, isoleucine, methionine
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
-
-
-
?
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
-
?
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
-
?
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
kinetic mechanism
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
essential step in amino acids L-methionine, L-threonine, and L-isoleucine biosynthesis
-
-
?
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
Thermophilic bacterium
-
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
-
-
r
L-aspartate 4-semialdehyde + NADPH
L-homoserine + NADP+
-
part of the aspartate pathway of amino acid biosynthesis
-
-
r
L-aspartate 4-semialdehyde + NADPH
L-homoserine + NADP+
-
-
-
r
L-aspartate 4-semialdehyde + NADPH + H+
L-homoserine + NADP+
-
-
-
-
?
L-aspartate 4-semialdehyde + NADPH + H+
L-homoserine + NADP+
Lactiplantibacillus plantarum NCIMB 8826
-
-
-
-
?
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
?
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
Thermophilic bacterium
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H + H+
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H + H+
Sulfurisphaera tokodaii DSM 16993 / JCM 10545 / NBRC 100140 / 7
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
Sulfurisphaera tokodaii DSM 16993 / JCM 10545 / NBRC 100140 / 7
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH
-
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
the binding of L-homoserine is the rate limiting factor for L-homoserine oxidation
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
the binding of L-homoserine is the rate limiting factor for L-homoserine oxidation
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
Candida albicans SC5314 / ATCC MYA-2876
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
no activity of the wild-type enzyme with NADP+, but only with enzyme mutants R40A and K57A
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
no activity of the wild-type enzyme with NADP+, but only with enzyme mutants R40A and K57A
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
additional information
?
-
enzyme BsHSD exclusively prefers NADP+ to NAD+
-
-
-
additional information
?
-
-
enzyme BsHSD exclusively prefers NADP+ to NAD+
-
-
-
additional information
?
-
enzyme BsHSD exclusively prefers NADP+ to NAD+
-
-
-
additional information
?
-
the bifunctional enzyme also exhibits aspartokinase activity, EC 2.7.2.4
-
-
-
additional information
?
-
the bifunctional enzyme also exhibits aspartokinase activity, EC 2.7.2.4
-
-
-
additional information
?
-
enzyme does not show aspartate kinase activity
-
-
?
additional information
?
-
enzyme does not show aspartate kinase activity
-
-
?
additional information
?
-
enzyme does not show aspartate kinase activity
-
-
?
additional information
?
-
-
enzyme does not show aspartate kinase activity
-
-
?
additional information
?
-
the bifunctional enzyme also exhibits aspartokinase (AK) activity, EC 2.7.2.4. It shows substantial activities of both AK and homoserine dehydrogenase (HseDH)
-
-
-
additional information
?
-
-
the bifunctional enzyme also exhibits aspartokinase (AK) activity, EC 2.7.2.4. It shows substantial activities of both AK and homoserine dehydrogenase (HseDH)
-
-
-
additional information
?
-
the bifunctional enzyme also exhibits aspartokinase (AK) activity, EC 2.7.2.4. It shows substantial activities of both AK and homoserine dehydrogenase (HseDH)
-
-
-
additional information
?
-
the bifunctional enzyme also exhibits aspartokinase (AK) activity, EC 2.7.2.4. It shows substantial activities of both AK and homoserine dehydrogenase (HseDH)
-
-
-
additional information
?
-
the bifunctional enzyme also exhibits aspartokinase (AK) activity, EC 2.7.2.4. It shows substantial activities of both AK and homoserine dehydrogenase (HseDH)
-
-
-
additional information
?
-
substrates binding modes, overview
-
-
-
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
L-aspartate 4-semialdehyde + NADPH
L-homoserine + NADP+
-
part of the aspartate pathway of amino acid biosynthesis
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
kinetic mechanism
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
third reaction in the pathway between aspartate and the amino acids threonine, isoleucine, methionine
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
third reaction in the pathway between aspartate and the amino acids threonine, isoleucine, methionine
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
kinetic mechanism
-
-
r
L-aspartate 4-semialdehyde + NAD(P)H
L-homoserine + NAD(P)+
-
essential step in amino acids L-methionine, L-threonine, and L-isoleucine biosynthesis
-
-
?
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H + H+
-
-
-
r
L-homoserine + NAD(P)+
L-aspartate 4-semialdehyde + NAD(P)H + H+
Sulfurisphaera tokodaii DSM 16993 / JCM 10545 / NBRC 100140 / 7
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
r
L-homoserine + NAD+
L-aspartate 4-semialdehyde + NADH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
Candida albicans SC5314 / ATCC MYA-2876
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
r
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
L-homoserine + NADP+
L-aspartate 4-semialdehyde + NADPH + H+
-
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
NADP does not act as a cofactor for this enzyme, but as a strong inhibitor of NAD+-dependent oxidation of Hse, analysis of the cofactor-binding site of the enzyme, Pyrococcus horikoshii HseDH shows a unique cofactor binding mode, which is not observed in conventional NAD(P)-dependent dehydrogenases. Superposition of the Hse/NADPH-bound K57A structure onto the NADPH-bound wild-type structure shows that the NADPH molecule in the mutant structure is positioned/configured nearly identically to the NADPH molecule in the wild-type structure, except for the positioning of the C2 phosphate group of the adenine ribose. The C2 phosphate is tightly held in position through five surrounding hydrogen bonds in the wild-type enzyme. In K57A mutant the C2 phosphate group is rotates in a clockwise direction around C2B of NADPH by about 30° relative to the wild-type structure. The guanidino group of Arg40 in the mutant is also rotated clockwise by about 90° around the NE atom of Arg40 relative to the wild-type structure
-
NADH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADH
GmHSD displays a 1.6fold preference for NADPH over NADH as the cofactor in the oxidation reaction. In the reduction reaction NADP+ is favored nearly 4fold as the cofactor
NADP+
no activity of the wild-type enzyme with NADP+, but only with enzyme mutants R40A and K57A
NADP+
StHSD also exhibits activity with NADP+, but with much lower efficiency compared to NAD+
NADPH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADPH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADPH
-
threonine sensitive isozyme can use NADPH or NADH, threonine insensitive isozyme can use NADPH only
NADPH
GmHSD displays a 1.6fold preference for NADPH over NADH as the cofactor in the oxidation reaction. In the reduction reaction NADP+ is favored nearly 4fold as the cofactor
NADPH
no activity of the wild-type enzyme with NADPH, but only with enzyme mutants R40A and K57A
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Cs+
K+
Li+
Mg2+
Na+
NH4+
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-[(1S,2S)-2-(bromomethyl)cyclopropyl]-4-[(trifluoromethyl)sulfanyl]benzene
-
2,2'-[thiobis[[2-(1,1-dimethylethyl)-5-methyl-4,1-phenylene]oxy]]bis-acetic acid diethyl ester
-
-
4,4'-[1,2-ethanediylbis(thio)]bis[2,6-bis(1-methylpropyl)]-phenol
-
-
4,4'-[1,2-ethanediylbis(thio)]bis[2-(1,1-dimethylethyl)-6-methyl]-phenol
-
-
4-[[[4-(1,1-dimethylethyl)phenyl]thio]methyl]-2,6-bis(1-methylethyl)-phenol
-
-
5-hydroxy-4-oxo-L-norvaline
HONV, the mechanism of antifungal action of HONV dipeptides (determined against Candida albicans strain ATCC 10231 cells in three different growth media) involves uptake by the oligopeptide transport system, subsequent intracellular cleavage by cytosolic peptidases, and inhibition of homoserine dehydrogenase by the released HONV. Chemical synthesis of HONV and construction of HONV dipeptides as potential antifungal agents, overview. Six dipeptides with L-alanine, L-valine, L-norvaline (Nva), L-leucine, L-isoleucine, and L-phenylalanine as the N-terminal residues are obtained, Gly-HONV and D-Leu-HONV are synthesized and evaluated for comparative purposes. Antifungal in vitro activity and MIC values of HONV and its dipeptides, overview. Activity of HONV strongly depends on growth medium composition. Dipeptide (S)-2-N-[(R)-leucyl]amino-5-hydroxy-4-oxopentanoic acid (D-Leu-HONV) is inactive in all growth media. Antifungal activity of the compounds against different Candida species. Lack of activity of HONV-containing dipeptides against the Candida albicans opt1-opt5DELTA ptr2DELTA ptr22DELTA mutant clearly indicates that these compounds are transported to Candida albicans cells by the oligopeptide transport system, most probably by the di-tripeptide permeases Ptr2p and Ptr22, uptake rates into Candida albicans strain ATCC 10231 cells at pH 5.0 and pH 7.0 are determined, the initial uptake velocities are generally higher at pH 5.0 than at pH 7.0
glycyl-5-hydroxy-4-oxo-L-norvaline
i.e. (S)-2-N-glycylamino-5-hydroxy-4-oxopentanoic acid
L-alanyl-5-hydroxy-4-oxo-L-norvaline
i.e. (S)-2-N-[(S)-alanyl]amino-5-hydroxy-4-oxopentanoic acid
L-isoleucyl-5-hydroxy-4-oxo-L-norvaline
i.e. (S)-2-N-[(S)-isoleucyl]amino-5-hydroxy-4-oxopentanoic acid
L-lysine
allosteric regulation of recombinant engineered homoserine dehydrogenase by nonnatural inhibitor L-lysine
L-norvalyl-5-hydroxy-4-oxo-L-norvaline
i.e. (S)-2-N-[(S)-norvalyl]amino-5-hydroxy-4-oxopentanoic acid
L-phenylalanyl-5-hydroxy-4-oxo-L-norvaline
i.e. (S)-2-N-[(S)-phenylalanyl]amino-5-hydroxy-4-oxopentanoic acid
L-valyl-5-hydroxy-4-oxo-L-norvaline
i.e. (S)-2-N-[(S)-valyl]amino-5-hydroxy-4-oxopentanoic acid
NADH
acts as a competitive inhibitor of NAD+, product inhibition, non-competitive inhibition versus L-homoserine
[2-(1,1-dimethylethyl)-4-[[5-(1,1-dimethylethyl)-4-hydroxy-2-methylphenyl]thio]-5-methylphenoxy]-acetic acid ethyl ester
-
-
4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol
competitive to L-aspartate 4-semialdehyde, enzyme binding structure anaysis from crystal structure, overview
Amphotericin B
MIC value against strain Pb18 is 0.12 mg/ml
itraconazole
MIC value against strain Pb18 is 0.007 mg/ml
L-cysteine
-
slight inhibition of chloroplast isozyme, strong inhibition of cytoplasmic isozyme
L-cysteine
-
slight inhibition of chloroplast isozyme, strong inhibition of cytoplasmic isozyme
L-cysteine
competitive versus L-homoserine, uncompetitive versus cofactors NAD+ and NADP+. 95% inhibition at 10 mM. The feedback inhibition of StHSD by cysteine occurs through the formation of an enzyme-NAD-cysteine complex. Cysteine situates within the homoserine binding site, formation of a covalent bond between cysteine and the nicotinamide ring. Cysteine interacts with six residues (Gly156, Thr157, Tyr183, Glu185, Asp191, and Lys200) in the StHSD active site, binding structure analysis, overview
L-threonine
strong inhibition of both enzyme activities, aspartate dehydrogenase and aspartate kinase activity, by decreasing the affinity of the enzyme for substrate and cofactors, kinetic effects
L-threonine
-
the regulatory domain of the enzyme contains 2 binding sites, interaction with Gln443 leads to inhibition of the aspartate kinase activity and facilitates the binding of a second threonine on Gln524 leading to inhibition of the homoserine dehydrogenase activity, inhibition of the forward reactions
L-threonine
the enzyme activity is subjected to feedback regulation by L-threonine
L-threonine
the natural threonine binding sites of the enzyme are predicted and verified by mutagenesis experiments
L-threonine
-
degree of inhibition depends on age of plant; sensitive and insensitive isozymes
L-threonine
-
degree of inhibition depends on age of plant; sensitive and insensitive isozymes
L-threonine
-
degree of inhibition depends on age of plant; sensitive and insensitive isozymes
NADP+
NADP+ does not act as a cofactor for this enzyme, but as a strong inhibitor of NAD+-dependent oxidation of Hse, evaluation of the factors responsible for the NADP+-mediated inhibition
threonine
-
feedback inhibition, one isozyme is resistant and another is sensitive to threonine inhibition, 46.9% inhibition at 1 mM, 63.9% at 5 mM
threonine
-
the methionine-producing strain contains a deregulated homoserine dehydrogenase that is not sensitive to feedback inhibition as the wild-type enzyme
Zinc273730
MIC value is 0.064. Zinc273730 makes important contacts with Gly215, Tyr216, Thr217, and Glu218
additional information
-
Lys, Met, and S-2-aminoethyl-L-cysteine do not affect HSDH activity at 1-5 mM
-
additional information
the natural threonine binding sites of the enzyme are engineered to a lysine binding pocket. The reengineered enzyme only responds to lysine inhibition but not to threonine
-
additional information
-
the natural threonine binding sites of the enzyme are engineered to a lysine binding pocket. The reengineered enzyme only responds to lysine inhibition but not to threonine
-
additional information
L-homoserine inhibits the activity of aspartokinase encoded by metL
-
additional information
enzyme is not inhibited by other aspartate-derived amino acids than threonine
-
additional information
enzyme is not inhibited by other aspartate-derived amino acids than threonine
-
additional information
enzyme is not inhibited by other aspartate-derived amino acids than threonine
-
additional information
-
enzyme is not inhibited by other aspartate-derived amino acids than threonine
-
additional information
-
Thr does not inhibit homoserine dehydrogenase 1
-
additional information
molecular docking simulations and inhibitor screening, virtual screening simulations with 187841 molecules purchasable from the Zinc database. 14 molecules are selected and analyzed by the use of absorption, distribution, metabolism, excretion, and toxicity criteria, resulting in four compounds for in vitro assays. Synergistic effects of HS1 and HS2 in combination with itraconazole against Paracoccidioides brasiliensis. Zinc1531037 and Zinc52986906 are not inhibitory
-
additional information
-
molecular docking simulations and inhibitor screening, virtual screening simulations with 187841 molecules purchasable from the Zinc database. 14 molecules are selected and analyzed by the use of absorption, distribution, metabolism, excretion, and toxicity criteria, resulting in four compounds for in vitro assays. Synergistic effects of HS1 and HS2 in combination with itraconazole against Paracoccidioides brasiliensis. Zinc1531037 and Zinc52986906 are not inhibitory
-
additional information
PbHSD inhibitor screening using the Zinc library, molecular dynamics simulations of PbHSD and ligand docking, electrostatic contacts between protein residues and the respective ligand atoms, overview. The selected ligands remain bound to the protein by a common mechanism throughout the simulation. Cytotoxicity evaluation in HeLa and Vero cells
-
additional information
-
PbHSD inhibitor screening using the Zinc library, molecular dynamics simulations of PbHSD and ligand docking, electrostatic contacts between protein residues and the respective ligand atoms, overview. The selected ligands remain bound to the protein by a common mechanism throughout the simulation. Cytotoxicity evaluation in HeLa and Vero cells
-
additional information
molecular docking simulations and inhibitor screening, virtual screening simulations with 187841 molecules purchasable from the Zinc database. 14 Molecules are selected and analyzed by the use of absorption, distribution, metabolism, excretion, and toxicity criteria, resulting in four compounds for in vitro assays. Zinc1531037 and Zinc52986906 are not inhibitory
-
additional information
-
molecular docking simulations and inhibitor screening, virtual screening simulations with 187841 molecules purchasable from the Zinc database. 14 Molecules are selected and analyzed by the use of absorption, distribution, metabolism, excretion, and toxicity criteria, resulting in four compounds for in vitro assays. Zinc1531037 and Zinc52986906 are not inhibitory
-
additional information
-
no inhibition by [2-(1,1-dimethylethyl)-4-[[5-(1,1-dimethylethyl)-4-hydroxy-2-methylphenyl]thio]-5-methylphenoxy]-acetic acid and 4-amino-butyric acid 2-tert-butyl-4-(3-tert-butyl-4-hydroxy-phenylsulfanyl)-phenyl ester
-
additional information
tHSD is poorly inhibited by less than 5% by 10 mM L-methionine, L-isoleucine, or L-threonine, all of which are final products in the aspartate pathway, and by L-lysine
-
additional information
-
tHSD is poorly inhibited by less than 5% by 10 mM L-methionine, L-isoleucine, or L-threonine, all of which are final products in the aspartate pathway, and by L-lysine
-
additional information
L-homoserine oxidation of the Thermotoga maritima enzyme is almost impervious to inhibition by L-threonine, while L-threonine inhibits AK activity in a cooperative manner. The distinctive sequence of the regulatory domain in Thermotoga maritima AK-HseDH is likely responsible for the unique sensitivity to L-threonine. The quaternary structure of this enzyme is not affected by L-threonine
-
additional information
-
L-homoserine oxidation of the Thermotoga maritima enzyme is almost impervious to inhibition by L-threonine, while L-threonine inhibits AK activity in a cooperative manner. The distinctive sequence of the regulatory domain in Thermotoga maritima AK-HseDH is likely responsible for the unique sensitivity to L-threonine. The quaternary structure of this enzyme is not affected by L-threonine
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dithiothreitol
the enzyme is 2.5fold activated by the addition of 0.8 mM dithiothreitol. The activation is caused by cleavage of the disulfide bond formed between two cysteine residues in the C-terminal regions of the two subunits
additional information
the HSD from the hyperthermophilic archaeon Sulfolobus tokodaii (StHSD) is activated by reductive cleavage of the disulfide bond formed between cysteine residues (Cys304) in the C-terminal regions of the homodimer subunits
-
additional information
-
the HSD from the hyperthermophilic archaeon Sulfolobus tokodaii (StHSD) is activated by reductive cleavage of the disulfide bond formed between cysteine residues (Cys304) in the C-terminal regions of the homodimer subunits
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Cysts
A physical map of a gene-dense region in soybean linkage group A2 near the black seed coat and Rhg (4) loci.
homoserine dehydrogenase deficiency
Effects of Homoserine Dehydrogenase Deficiency on Production of Cytidine by Mutants of Bacillus subtilis.
Infections
Biochemical characterization and redesign of the coenzyme specificity of a novel monofunctional NAD+-dependent homoserine dehydrogenase from the human pathogen Neisseria gonorrhoeae.
Infections
Identification of Human Junctional Adhesion Molecule 1 as a Functional Receptor for the Hom-1 Calicivirus on Human Cells.
Mycoses
Targeting the Homoserine Dehydrogenase of Paracoccidioides Species for Treatment of Systemic Fungal Infections.
Paracoccidioidomycosis
Targeting the Homoserine Dehydrogenase of Paracoccidioides Species for Treatment of Systemic Fungal Infections.
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
11.6
L-aspartate
pH 8.0, 37°C, purified recombinant soluble enzyme
0.098
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
0.15
L-aspartate 4-semialdehyde
-
threonine-resistant enzyme, pH and temperature not specified in the publication
0.25
L-aspartate 4-semialdehyde
-
threonine-sensitive enzyme, pH and temperature not specified in the publication
0.569
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
0.845
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
1.19
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
1.25
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
2.19
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
0.41
L-homoserine
-
recombinant hybrid bifunctional holoenzyme AKIII-HDHI+ containing the interface region, homoserine dehydrogenase activity
0.68
L-homoserine
-
recombinant isolated catalytic HDH-domain containing the interface region, homoserine dehydrogenase activity
1.2
L-homoserine
-
recombinant wild-type bifunctional holoenzyme, homoserine dehydrogenase activity
5.2
L-homoserine
pH 8.0, 37°C, purified recombinant soluble enzyme
17.2
L-homoserine
-
recombinant isolated catalytic HDH-domain not containing the interface region, homoserine dehydrogenase activity
0.46
NADH
-
isoenzyme II, at pH 7.5, temperature not specified in the publication
0.036
NADPH
-
threonine-resistant enzyme, pH and temperature not specified in the publication
0.04
NADPH
-
threonine-sensitive enzyme, pH and temperature not specified in the publication
additional information
additional information
Michaelis-Menten steady-state kinetics
-
additional information
additional information
-
Michaelis-Menten steady-state kinetics
-
additional information
additional information
enzyme HseDH shows typical Michaelis-Menten kinetics for oxidation
-
additional information
additional information
kinetic profile
-
additional information
additional information
the binding of L-homoserine is the rate limiting factor for L-homoserine oxidation, Michaelis-Menten kinetics, overview
-
additional information
additional information
-
the binding of L-homoserine is the rate limiting factor for L-homoserine oxidation, Michaelis-Menten kinetics, overview
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2.8
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
9.68
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
11.58
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
12.98
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
19.3
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
22.58
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
24
L-homoserine
-
recombinant hybrid bifunctional holoenzyme AKIII-HDHI+ containing the interface region, homoserine dehydrogenase activity
0.24
L-homoserine
-
recombinant wild-type bifunctional holoenzyme, homoserine dehydrogenase activity
0.51
L-homoserine
-
recombinant isolated catalytic HDH-domain not containing the interface region, homoserine dehydrogenase activity
3.3
L-homoserine
-
recombinant isolated catalytic HDH-domain containing the interface region, homoserine dehydrogenase activity
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5.29
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
10.39
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
16.22
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
17.02
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
26.73
L-aspartate 4-semialdehyde
cosubstrate NADH, pH 8.0, 25°C
28.54
L-aspartate 4-semialdehyde
cosubstrate NADPH, pH 8.0, 25°C
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0131
(2S)-2-[[4-(propan-2-yl)phenyl]sulfanyl]propanenitrile
pH and temperature not specified in the publication
0.01307
1-tert-butyl-4-[(difluoromethyl)sulfanyl]benzene
pH and temperature not specified in the publication
0.00963
1-[(1S,2S)-2-(bromomethyl)cyclopropyl]-4-[(trifluoromethyl)sulfanyl]benzene
pH and temperature not specified in the publication
0.01568
3-[(4-tert-butylphenyl)sulfanyl]propane-1-thiol
pH and temperature not specified in the publication
0.01
4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol
pH and temperature not specified in the publication
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0051
4-(4-hydroxy-3-isopropylphenylthio)-2-isopropylphenol
Mycobacterium leprae
pH and temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.0044 - 0.0046
-
enzyme activity at different seed developmental stages, overview
1.48 - 2.01
purified recombinant enzyme expressed in Escherichia coli, pH 9.0, 25°C
18.87
purified recombinant soluble enzyme, reverse reaction of homoserine dehydrogenase
5.4
purified recombinant soluble enzyme, forward reaction of aspartate kinase
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
8.5
the catalytic activity of the enzyme for the conversion of L-homoserine to L-aspartate 4-semialdehyde (the reverse reaction) is enhanced at basic pH
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.5 - 11
over 60% of maximal activity within this range, profile overview
7 - 9.5
BsHSD is maximally active in L-HSE oxidation at pH 9.0 and is the least active at pH 7.0 with only 1.1% of the maximal activity
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
37
70
additional information
-
above 50°C temperature dependent conformational change
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25 - 50
45% of maximal activity at 25°C and 50°C, maximal activity at 35-40°C, 75% at 45°C, 65% at 35°C, profile overview
50 - 80
over 30% of maximal activity within this range, profile overview
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
bifunctional enzyme showing aspartate dehydrogenase and aspartate kinase activity
-
-
brenda
slightly modified at base 60 c to t, bas 1242 t to g, and base 1403 t to c, the latter modification results in change of Leu468 to Ser; var. Columbia, bifunctional enzyme showing aspartate dehydrogenase and aspartate kinase activity
TREMBL
brenda
var. Bensheim showing threonine and methionine prototrophy, bifunctional enzyme showing aspartate dehydrogenase and aspartate kinase activity, gene akthr2
-
-
brenda
a methionine-producing strain carrying mutations in the hom and the thrB genes
-
-
brenda
bifunctional aspartokinase-homoserine dehydrogenase AK-HSD-1
UniProt
brenda
bifunctional aspartokinase-homoserine dehydrogenase AK-HSD-2
UniProt
brenda
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SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
-
akthr2 is not or time-restricted expressed in stem, gynoecium, and during seed formation
brenda
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LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
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GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
additional information
evolution
the catalytic region of the enzyme is unique, the nucleotide-binding domain conforms to the Rossmann fold-like conventional NAD(P)-dependent dehydrogenases
evolution
enzyme homoserine dehydrogenase (HSD) belongs to the family of oxidoreductases and is essential for the biosynthesis of threonine (Thr), methionine (Met), and lysine (Lys) in the metabolic pathway of fungi and plants
evolution
enzyme homoserine dehydrogenase (HSD) belongs to the family of oxidoreductases and is essential for the biosynthesis of threonine (Thr), methionine (Met), and lysine (Lys) in the metabolic pathway of fungi and plants
evolution
the orientation of the three domains in the bifunctional aspartate kinase-homoserine dehydrogenase (AK-HseDH) homologue found in Thermotoga maritima totally differs from those observed in previously known AK-HseDHs, the domains line up in the order HseDH, AK, and regulatory domain
evolution
-
enzyme homoserine dehydrogenase (HSD) belongs to the family of oxidoreductases and is essential for the biosynthesis of threonine (Thr), methionine (Met), and lysine (Lys) in the metabolic pathway of fungi and plants
-
evolution
-
the orientation of the three domains in the bifunctional aspartate kinase-homoserine dehydrogenase (AK-HseDH) homologue found in Thermotoga maritima totally differs from those observed in previously known AK-HseDHs, the domains line up in the order HseDH, AK, and regulatory domain
-
evolution
-
enzyme homoserine dehydrogenase (HSD) belongs to the family of oxidoreductases and is essential for the biosynthesis of threonine (Thr), methionine (Met), and lysine (Lys) in the metabolic pathway of fungi and plants
-
evolution
-
the catalytic region of the enzyme is unique, the nucleotide-binding domain conforms to the Rossmann fold-like conventional NAD(P)-dependent dehydrogenases
-
evolution
-
the orientation of the three domains in the bifunctional aspartate kinase-homoserine dehydrogenase (AK-HseDH) homologue found in Thermotoga maritima totally differs from those observed in previously known AK-HseDHs, the domains line up in the order HseDH, AK, and regulatory domain
-
evolution
-
the orientation of the three domains in the bifunctional aspartate kinase-homoserine dehydrogenase (AK-HseDH) homologue found in Thermotoga maritima totally differs from those observed in previously known AK-HseDHs, the domains line up in the order HseDH, AK, and regulatory domain
-
malfunction
HOM6 deletions cause translational arrest in cells grown under amino acid starvation conditions. HOM6 deletion reduces Candida albicans cell adhesion to polystyrene, which is a common plastic used in many medical devices. HOM6-homozygous mutants are hypersensitive to hygromycin B and cycloheximide as compared with wild-type, HOM6-heterozygous, and HOM6-reintegrated strains. HOM6 deletion affects translation and leads to the accumulation of free ribosomes
malfunction
the chemical mutagen ENU causes a mutation in the homoserine serine dehydrogenase enzyme which diverted the aspartyl-beta-semialdehyde to bind with 2,3-dihydrodipicolinate synthase to participate in the L-lysine synthesis through 2,3 meso-diaminopimelate (Meso-Dap). Being a recombinant for diaminopimelate dehydrogenase (ddh), the auxotrophic mutant for the homoserine dehydrogenase follows the ddh pathway by overexpression of ddh by deviating the acetyltransferase and succinyl transferase is the reason for the high yield of L-lysine production
malfunction
-
the chemical mutagen ENU causes a mutation in the homoserine serine dehydrogenase enzyme which diverted the aspartyl-beta-semialdehyde to bind with 2,3-dihydrodipicolinate synthase to participate in the L-lysine synthesis through 2,3 meso-diaminopimelate (Meso-Dap). Being a recombinant for diaminopimelate dehydrogenase (ddh), the auxotrophic mutant for the homoserine dehydrogenase follows the ddh pathway by overexpression of ddh by deviating the acetyltransferase and succinyl transferase is the reason for the high yield of L-lysine production
-
malfunction
-
the chemical mutagen ENU causes a mutation in the homoserine serine dehydrogenase enzyme which diverted the aspartyl-beta-semialdehyde to bind with 2,3-dihydrodipicolinate synthase to participate in the L-lysine synthesis through 2,3 meso-diaminopimelate (Meso-Dap). Being a recombinant for diaminopimelate dehydrogenase (ddh), the auxotrophic mutant for the homoserine dehydrogenase follows the ddh pathway by overexpression of ddh by deviating the acetyltransferase and succinyl transferase is the reason for the high yield of L-lysine production
-
malfunction
-
the chemical mutagen ENU causes a mutation in the homoserine serine dehydrogenase enzyme which diverted the aspartyl-beta-semialdehyde to bind with 2,3-dihydrodipicolinate synthase to participate in the L-lysine synthesis through 2,3 meso-diaminopimelate (Meso-Dap). Being a recombinant for diaminopimelate dehydrogenase (ddh), the auxotrophic mutant for the homoserine dehydrogenase follows the ddh pathway by overexpression of ddh by deviating the acetyltransferase and succinyl transferase is the reason for the high yield of L-lysine production
-
malfunction
-
the chemical mutagen ENU causes a mutation in the homoserine serine dehydrogenase enzyme which diverted the aspartyl-beta-semialdehyde to bind with 2,3-dihydrodipicolinate synthase to participate in the L-lysine synthesis through 2,3 meso-diaminopimelate (Meso-Dap). Being a recombinant for diaminopimelate dehydrogenase (ddh), the auxotrophic mutant for the homoserine dehydrogenase follows the ddh pathway by overexpression of ddh by deviating the acetyltransferase and succinyl transferase is the reason for the high yield of L-lysine production
-
malfunction
Candida albicans SC5314 / ATCC MYA-2876
-
HOM6 deletions cause translational arrest in cells grown under amino acid starvation conditions. HOM6 deletion reduces Candida albicans cell adhesion to polystyrene, which is a common plastic used in many medical devices. HOM6-homozygous mutants are hypersensitive to hygromycin B and cycloheximide as compared with wild-type, HOM6-heterozygous, and HOM6-reintegrated strains. HOM6 deletion affects translation and leads to the accumulation of free ribosomes
-
malfunction
-
the chemical mutagen ENU causes a mutation in the homoserine serine dehydrogenase enzyme which diverted the aspartyl-beta-semialdehyde to bind with 2,3-dihydrodipicolinate synthase to participate in the L-lysine synthesis through 2,3 meso-diaminopimelate (Meso-Dap). Being a recombinant for diaminopimelate dehydrogenase (ddh), the auxotrophic mutant for the homoserine dehydrogenase follows the ddh pathway by overexpression of ddh by deviating the acetyltransferase and succinyl transferase is the reason for the high yield of L-lysine production
-
malfunction
-
the chemical mutagen ENU causes a mutation in the homoserine serine dehydrogenase enzyme which diverted the aspartyl-beta-semialdehyde to bind with 2,3-dihydrodipicolinate synthase to participate in the L-lysine synthesis through 2,3 meso-diaminopimelate (Meso-Dap). Being a recombinant for diaminopimelate dehydrogenase (ddh), the auxotrophic mutant for the homoserine dehydrogenase follows the ddh pathway by overexpression of ddh by deviating the acetyltransferase and succinyl transferase is the reason for the high yield of L-lysine production
-
metabolism
homoserine dehydrogenase (HSD) is an oxidoreductase in the aspartic acid pathway. The L-homoserine produced by this enzyme at the first branch point of the aspartic acid pathway is a precursor for essential amino acids such as L-threonine, L-methionine and L-isoleucine
metabolism
homoserine dehydrogenase (HSD) is an oxidoreductase that is involved in the reversible conversion of L-aspartate semialdehyde to L-homoserine in a dinucleotide cofactor-dependent reduction reaction. HSD is thus a crucial intermediate enzyme linked to the biosynthesis of several essential amino acids such as lysine, methionine, isoleucine and threonine
metabolism
homoserine dehydrogenase activity and is involved in the biosynthesis of methionine and threonine
metabolism
homoserine dehydrogenase is a key enzyme in the L-threonine pathway
metabolism
biosynthetic pathway from L-aspartate to L-homoserine involving the bifunctional enzyme, overview
metabolism
homoserine dehydrogenase (HSD) catalyzes the reversible conversion of L-aspartate-4-semialdehyde to L-homoserine in the aspartate pathway for the biosynthesis of lysine, methionine, threonine, and isoleucine
metabolism
-
homoserine dehydrogenase (HSD) catalyzes the reversible conversion of L-aspartate-4-semialdehyde to L-homoserine in the aspartate pathway for the biosynthesis of lysine, methionine, threonine, and isoleucine
-
metabolism
-
biosynthetic pathway from L-aspartate to L-homoserine involving the bifunctional enzyme, overview
-
metabolism
-
homoserine dehydrogenase (HSD) is an oxidoreductase in the aspartic acid pathway. The L-homoserine produced by this enzyme at the first branch point of the aspartic acid pathway is a precursor for essential amino acids such as L-threonine, L-methionine and L-isoleucine
-
metabolism
-
homoserine dehydrogenase (HSD) is an oxidoreductase that is involved in the reversible conversion of L-aspartate semialdehyde to L-homoserine in a dinucleotide cofactor-dependent reduction reaction. HSD is thus a crucial intermediate enzyme linked to the biosynthesis of several essential amino acids such as lysine, methionine, isoleucine and threonine
-
metabolism
-
homoserine dehydrogenase is a key enzyme in the L-threonine pathway
-
metabolism
Candida albicans SC5314 / ATCC MYA-2876
-
homoserine dehydrogenase activity and is involved in the biosynthesis of methionine and threonine
-
metabolism
-
biosynthetic pathway from L-aspartate to L-homoserine involving the bifunctional enzyme, overview
-
metabolism
-
biosynthetic pathway from L-aspartate to L-homoserine involving the bifunctional enzyme, overview
-
physiological function
contrary to wild-type MGA3 cells that secrete 0.4 g/l L-lysine and 59 g/l L-glutamate under optimised fed batch methanol fermentation, the hom-1 mutant M168-20 secretes 11 g/l L-lysine and 69 g/l of L-glutamate. Overproduction of pyruvate carboxylase and its mutant enzyme P455S in M168-20 has no positive effect on the volumetric L-lysine yield and the L-lysine yield on methanol, and causes significantly reduced volumetric L-glutamate yield and L-glutamate yield on methanol
physiological function
homoserine dehydrogenase catalyzes an NAD(P)-dependent reversible reaction between L-homoserine and aspartate 4-semialdehyde and is involved in the aspartate pathway
physiological function
the enzyme coordinates a critical branch point of the metabolic pathway that leads to the synthesis of bacterial cell-wall components such as L-lysine and m-DAP in addition to other amino acids such as L-threonine, L-methionine and L-isoleucine. The kinetic behaviour of Staphylococcus aureus HSD is not altered in the presence of plausible allosteric inhibitors such as L-threonine and L-serine
physiological function
the enzyme is involved in cell-wall maintenance and essential amino acid biosynthesis. Homoserine dehydrogenase catalyzes a reaction at the branch point of the pathway leading to lysine biosynthesis. This pathway is also referred to as the diaminopimelate (dap) pathway
physiological function
the enzyme is naturally allosterically regulated by threonine and isoleucine
physiological function
aspartate kinase (AK, EC 2.7.2.4) and homoserine dehydrogenase (HseDH) are involved in the biosynthetic pathway from L-aspartate to L-homoserine (Hse) in plants and microorganisms. Hse is a common precursor for the synthesis of L-methionine, L-threonine, and L-isoleucine. At the first step in this pathway, L-aspartate is phosphorylated to beta-aspartyl phosphate (beta-Ap) by AK
physiological function
homoserine dehydrogenase (HSD) is an important regulatory enzyme in the aspartate pathway, which mediates synthesis of methionine, threonine and isoleucine from aspartate
physiological function
the homoserine dehydrogenase enzyme is essentially required for the biosynthesis of methionine, threonine, and isoleucine in fungi
physiological function
-
aspartate kinase (AK, EC 2.7.2.4) and homoserine dehydrogenase (HseDH) are involved in the biosynthetic pathway from L-aspartate to L-homoserine (Hse) in plants and microorganisms. Hse is a common precursor for the synthesis of L-methionine, L-threonine, and L-isoleucine. At the first step in this pathway, L-aspartate is phosphorylated to beta-aspartyl phosphate (beta-Ap) by AK
-
physiological function
-
homoserine dehydrogenase (HSD) is an important regulatory enzyme in the aspartate pathway, which mediates synthesis of methionine, threonine and isoleucine from aspartate
-
physiological function
-
the homoserine dehydrogenase enzyme is essentially required for the biosynthesis of methionine, threonine, and isoleucine in fungi
-
physiological function
-
the enzyme coordinates a critical branch point of the metabolic pathway that leads to the synthesis of bacterial cell-wall components such as L-lysine and m-DAP in addition to other amino acids such as L-threonine, L-methionine and L-isoleucine. The kinetic behaviour of Staphylococcus aureus HSD is not altered in the presence of plausible allosteric inhibitors such as L-threonine and L-serine
-
physiological function
-
the enzyme is involved in cell-wall maintenance and essential amino acid biosynthesis. Homoserine dehydrogenase catalyzes a reaction at the branch point of the pathway leading to lysine biosynthesis. This pathway is also referred to as the diaminopimelate (dap) pathway
-
physiological function
Sulfurisphaera tokodaii DSM 16993 / JCM 10545 / NBRC 100140 / 7
-
homoserine dehydrogenase catalyzes an NAD(P)-dependent reversible reaction between L-homoserine and aspartate 4-semialdehyde and is involved in the aspartate pathway
-
physiological function
-
aspartate kinase (AK, EC 2.7.2.4) and homoserine dehydrogenase (HseDH) are involved in the biosynthetic pathway from L-aspartate to L-homoserine (Hse) in plants and microorganisms. Hse is a common precursor for the synthesis of L-methionine, L-threonine, and L-isoleucine. At the first step in this pathway, L-aspartate is phosphorylated to beta-aspartyl phosphate (beta-Ap) by AK
-
physiological function
-
aspartate kinase (AK, EC 2.7.2.4) and homoserine dehydrogenase (HseDH) are involved in the biosynthetic pathway from L-aspartate to L-homoserine (Hse) in plants and microorganisms. Hse is a common precursor for the synthesis of L-methionine, L-threonine, and L-isoleucine. At the first step in this pathway, L-aspartate is phosphorylated to beta-aspartyl phosphate (beta-Ap) by AK
-
physiological function
-
contrary to wild-type MGA3 cells that secrete 0.4 g/l L-lysine and 59 g/l L-glutamate under optimised fed batch methanol fermentation, the hom-1 mutant M168-20 secretes 11 g/l L-lysine and 69 g/l of L-glutamate. Overproduction of pyruvate carboxylase and its mutant enzyme P455S in M168-20 has no positive effect on the volumetric L-lysine yield and the L-lysine yield on methanol, and causes significantly reduced volumetric L-glutamate yield and L-glutamate yield on methanol
-
additional information
structural basis for the catalytic mechanism of homoserine dehydrogenase, the cofactor-binding site and catalytic site are docked with the cofactor NADP+ and L-homoserine, respectively, modelling, overview
additional information
-
structural basis for the catalytic mechanism of homoserine dehydrogenase, the cofactor-binding site and catalytic site are docked with the cofactor NADP+ and L-homoserine, respectively, modelling, overview
additional information
structure homology modelling using the template, homoserine dehydrogenase from Thiobacillus denitrificans, PDB ID 3MTJ, three-dimensional structure analysis and molecular dynamics simulation, overview. Identification of substrate- and cofactor-binding regions. In L-aspartate semialdehyde binding, the substrate docks to the protein involving residues Thr163, Asp198, and Glu192, which may be important because they form a hydrogen bond with the enzyme. Key recognition residues are Lys107 and Lys207
additional information
binding of L-Hse and NADPH induces the conformational changes of TtHSD from an open to a closed form: the mobile loop containing Glu180 approaches to fix L-Hse and NADPH, and both Lys99 and Lys195 make hydrogen bonds with the hydroxy group of L-Hse. The ternary complex of TtHSDs in the closed form mimicks a Michaelis complex better than the previously reported open form structures from other species. Lys99 seems to be the acidx02base catalytic residue of HSD. The substrate L-Hse and the nicotinamide-ribose moiety of the cofactor NADPH are bound to a crevice formed at the interface between the substrate and nucleotide binding domains. In contrast, the adenosine group of NADPH is located at the surface of the enzyme. The open-closed conformational change may play an important role in the formation of the enzymex02substrate-cofactor complex and subsequent enzymatic catalysis
additional information
-
binding of L-Hse and NADPH induces the conformational changes of TtHSD from an open to a closed form: the mobile loop containing Glu180 approaches to fix L-Hse and NADPH, and both Lys99 and Lys195 make hydrogen bonds with the hydroxy group of L-Hse. The ternary complex of TtHSDs in the closed form mimicks a Michaelis complex better than the previously reported open form structures from other species. Lys99 seems to be the acidx02base catalytic residue of HSD. The substrate L-Hse and the nicotinamide-ribose moiety of the cofactor NADPH are bound to a crevice formed at the interface between the substrate and nucleotide binding domains. In contrast, the adenosine group of NADPH is located at the surface of the enzyme. The open-closed conformational change may play an important role in the formation of the enzymex02substrate-cofactor complex and subsequent enzymatic catalysis
additional information
molecular docking analysis of aspartyl-beta-semi aldehyde with homoserine dehydrogenase, modeling
additional information
structure homology modeling of enzyme with bound substrate NAD+ and L-homoserine using the Saccharomyces cerevisiae enzyme (PDB ID 1EBU) as template, binding analysis, overview. The model with the best output is subjected to gradient minimization, redocking, and molecular dynamics simulation
additional information
-
structure homology modeling of enzyme with bound substrate NAD+ and L-homoserine using the Saccharomyces cerevisiae enzyme (PDB ID 1EBU) as template, binding analysis, overview. The model with the best output is subjected to gradient minimization, redocking, and molecular dynamics simulation
additional information
three-dimensional structure homology modeling using the crystal structure of HSD from Mycolicibacterium hassiacum (PDB ID 6DZS) as a template, overview
additional information
-
three-dimensional structure homology modeling using the crystal structure of HSD from Mycolicibacterium hassiacum (PDB ID 6DZS) as a template, overview
additional information
-
molecular docking analysis of aspartyl-beta-semi aldehyde with homoserine dehydrogenase, modeling
-
additional information
-
structure homology modelling using the template, homoserine dehydrogenase from Thiobacillus denitrificans, PDB ID 3MTJ, three-dimensional structure analysis and molecular dynamics simulation, overview. Identification of substrate- and cofactor-binding regions. In L-aspartate semialdehyde binding, the substrate docks to the protein involving residues Thr163, Asp198, and Glu192, which may be important because they form a hydrogen bond with the enzyme. Key recognition residues are Lys107 and Lys207
-
additional information
-
molecular docking analysis of aspartyl-beta-semi aldehyde with homoserine dehydrogenase, modeling
-
additional information
-
three-dimensional structure homology modeling using the crystal structure of HSD from Mycolicibacterium hassiacum (PDB ID 6DZS) as a template, overview
-
additional information
-
molecular docking analysis of aspartyl-beta-semi aldehyde with homoserine dehydrogenase, modeling
-
additional information
-
molecular docking analysis of aspartyl-beta-semi aldehyde with homoserine dehydrogenase, modeling
-
additional information
-
structure homology modeling of enzyme with bound substrate NAD+ and L-homoserine using the Saccharomyces cerevisiae enzyme (PDB ID 1EBU) as template, binding analysis, overview. The model with the best output is subjected to gradient minimization, redocking, and molecular dynamics simulation
-
additional information
-
structural basis for the catalytic mechanism of homoserine dehydrogenase, the cofactor-binding site and catalytic site are docked with the cofactor NADP+ and L-homoserine, respectively, modelling, overview
-
additional information
-
molecular docking analysis of aspartyl-beta-semi aldehyde with homoserine dehydrogenase, modeling
-
additional information
-
molecular docking analysis of aspartyl-beta-semi aldehyde with homoserine dehydrogenase, modeling
-
Show AA Sequence and Transmembrane Helices (48503 entries)
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PDB
SCOP
CATH
UNIPROT
ORGANISM
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MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
168000 - 174000
220000
320000
40000
470000
55000
70000
75000
470000
-
wild-type enzyme in absence of L-threonine, mutant enzymes Q443A and Q524A both in presence or absence of L-threonine, gel filtration
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SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
homodimer
homopentamer or homohexamer
tetramer
additional information
dimer
StHSD is composed of a nucleotide-binding region (residues 1-130 and 285-304), a dimerization region (residues 131-145 and 256-284), and a catalytic region (residues 146-255). Presence of a disulfide bond formed between two cysteine residues (position 304) in the C-terminal regions of the two subunits
dimer
-
StHSD is composed of a nucleotide-binding region (residues 1-130 and 285-304), a dimerization region (residues 131-145 and 256-284), and a catalytic region (residues 146-255). Presence of a disulfide bond formed between two cysteine residues (position 304) in the C-terminal regions of the two subunits
-
homodimer
-
2 * 36925, sequence calculation, 2 * 40000, SDS-PAGE
-
homodimer
the enzyme is a dimer in solution as well as in the crystal. Enzyme HSD from stapylococcus aureus is an elongated molecule with three domains: a nucleotide cofactor binding domain at the N-terminus, a central catalytic domain and a C-terminal ACT domain, structure overview
homodimer
-
the enzyme is a dimer in solution as well as in the crystal. Enzyme HSD from stapylococcus aureus is an elongated molecule with three domains: a nucleotide cofactor binding domain at the N-terminus, a central catalytic domain and a C-terminal ACT domain, structure overview
-
homodimer
Sulfurisphaera tokodaii DSM 16993 / JCM 10545 / NBRC 100140 / 7
-
dimeric enzyme structure, overview
-
homopentamer or homohexamer
x * 81000, recombinant enzyme, SDS-PAGE, x * 81433, sequence calculation
homopentamer or homohexamer
-
x * 81000, recombinant enzyme, SDS-PAGE, x * 81433, sequence calculation
-
homopentamer or homohexamer
-
x * 81000, recombinant enzyme, SDS-PAGE, x * 81433, sequence calculation
-
homopentamer or homohexamer
-
x * 81000, recombinant enzyme, SDS-PAGE, x * 81433, sequence calculation
-
tetramer
4 * 48300, about sequence calculation, 4 x 42800-48500, recombinant His-tagged enzyme, SDS-PAGE
tetramer
-
4 * 48300, about sequence calculation, 4 x 42800-48500, recombinant His-tagged enzyme, SDS-PAGE
-
additional information
-
primary and secondary structure comparison, the bifunctional enzyme contains 2 homologous subdomains defined by a common loop-alpha helix-loop-beta strand-loop-beta strand motif, the enzymes' regulatory domain is composed of 2 subdomains, amino acid residues 414-453 and 495-534
additional information
the unusual oligomeric assembly can be attributed to the additional C-terminal ACT domain of enzyme BsHSD. Circular dichroism spectroscopy analysis exhibits a typical pattern for alpha/beta proteins, the enzyme structure includes a Rossman fold. The enzyme's nucleotide-binding domain and substrate-binding domain are commonly found in all HSDs from any organism, but the C-terminal ACT domain is an additional regulatory domain that is present in only a subset of HSDs
additional information
-
the unusual oligomeric assembly can be attributed to the additional C-terminal ACT domain of enzyme BsHSD. Circular dichroism spectroscopy analysis exhibits a typical pattern for alpha/beta proteins, the enzyme structure includes a Rossman fold. The enzyme's nucleotide-binding domain and substrate-binding domain are commonly found in all HSDs from any organism, but the C-terminal ACT domain is an additional regulatory domain that is present in only a subset of HSDs
additional information
-
the unusual oligomeric assembly can be attributed to the additional C-terminal ACT domain of enzyme BsHSD. Circular dichroism spectroscopy analysis exhibits a typical pattern for alpha/beta proteins, the enzyme structure includes a Rossman fold. The enzyme's nucleotide-binding domain and substrate-binding domain are commonly found in all HSDs from any organism, but the C-terminal ACT domain is an additional regulatory domain that is present in only a subset of HSDs
-
additional information
structure homology modelling, three-dimensional structure analysis and molecular dynamics simulation, overview
additional information
-
structure homology modelling, three-dimensional structure analysis and molecular dynamics simulation, overview
-
additional information
-
structural basis for the catalytic mechanism of homoserine dehydrogenase, overview
additional information
structural basis for the catalytic mechanism of homoserine dehydrogenase, overview
additional information
-
structural basis for the catalytic mechanism of homoserine dehydrogenase, overview
-
additional information
enzyme TtHSD folds into a dimer with a noncrystallographic 2fold axis. The subunit comprises three conserved domains of HSDs and a flexible tail at the C-terminus. The nucleotide-binding domain (residues 1-119 and 288-309) assumes an alpha/beta Rossmann fold with five beta-strands and four alpha-helices. The dimerization domain (residues 120-140 and 261-287) comprises two alpha-helices and two beta-strands that interact with the corresponding domain of the other subunit of the dimer to form an alpha/beta structure with the four-stranded beta-sheet. The substrate-binding domain (residues 141-260) comprises four beta-strands and five alpha-helices. The flexible tail at the C-terminus (310-332) extends from the nucleotide-binding domain to the substrate-binding domain
additional information
-
enzyme TtHSD folds into a dimer with a noncrystallographic 2fold axis. The subunit comprises three conserved domains of HSDs and a flexible tail at the C-terminus. The nucleotide-binding domain (residues 1-119 and 288-309) assumes an alpha/beta Rossmann fold with five beta-strands and four alpha-helices. The dimerization domain (residues 120-140 and 261-287) comprises two alpha-helices and two beta-strands that interact with the corresponding domain of the other subunit of the dimer to form an alpha/beta structure with the four-stranded beta-sheet. The substrate-binding domain (residues 141-260) comprises four beta-strands and five alpha-helices. The flexible tail at the C-terminus (310-332) extends from the nucleotide-binding domain to the substrate-binding domain
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POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
proteolytic modification
the HSD from the hyperthermophilic archaeon Sulfolobus tokodaii (StHSD) is activated by reductive cleavage of the disulfide bond formed between cysteine residues (Cys304) in the C-terminal regions of the homodimer subunits
proteolytic modification
-
the HSD from the hyperthermophilic archaeon Sulfolobus tokodaii (StHSD) is activated by reductive cleavage of the disulfide bond formed between cysteine residues (Cys304) in the C-terminal regions of the homodimer subunits
-
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CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
for the purified ligand-free recombinant wild-type enzyme: sitting drop vapor diffusion method, mixing of 0.001 ml of 12.0 mg/ml protein solution with an equal volume of mother liquor composed of 0.1 M potassium phosphate, pH 6.2, and 20% MPD, 2 days, 20°C, for the homoserine-bound K57A mutant enzyme: sitting drop vapor diffusion method, mixing of 0.002 ml of 10 mg/ml protein solution containing 1 mM homoserine with 0.002 ml of mother liquor containing 16% polyethylene glycol monomethyl ether 2000 and 0.1 M citrate buffer, pH 6.5, 7 days, 20°C, X-ray diffraction structure determination and analysis at 2.3 A resolution, molecular replacement and modelling
10 mg/ml purified recombinant enzyme, in TAPS, pH 8.5, in complex with inhibitor 4,4'-thiobis[2-(1-methylethyl)-phenol] in a molar ratio of 1:1, precipitant solution contains either 0.1 CHES, pH 9.5, 35% PEG 600 or 0.1 M CHES, pH 8.5, 40% PEG 400, and 0.2 M NaCl, 0.005 ml protein complex solution are equilibrated against 0.7 ml of precipitant solution using sitting drop technique, 3 months, X-ray diffraction structure determination and analysis at 3.0 A resolution, modeling
-
purified enzyme, crystallization at different pH values in the range of pH 6.0-8.5, hanging drop and sitting drop methods of vapour diffusion, 8 mg/ml protein solution is mixed with reservoir solution, different conditions involving addition of 0.2 M magnesium acetate and PEG 3350 or 8000, and 3.5% glycerol, overview. X-ray diffraction structure determination and analysis at 2.1-2.2 A resolution
purified enzyme, crystallization at different pH values in the range of pH 6.0-8.5, X-ray diffraction structure determination and analysis at 2.1-2.2 A resolution
purified enzyme StHSD complexed with cysteine and NAD+, hanging drop vapour diffusion method, mixing of 0.002 ml of 5 mg/ml protein solution with 0.002 ml of reservoir solution containing 23% w/v PEG 3350, 0.2 M di-ammonium tartrate, 0.001 ml of 20 mM NAD+, and 0.001 ml of 100 mM cysteine, and equilibration against 0.1 ml of reservoir solution, 12°C, X-ray diffraction structure determination and analysis at 2.1 A resolution, molecular replacement using the StHSD structure (PDB ID 4YDR) as an initial phasing model
purified recombinant enzyme in oxidized and in reduced form, hanging drop vapor diffusion method, for the oxidized form: mixing of 0.0015 ml of 5.9 mg/ml protein solution with 0.0015 ml of reservoir solution, pH 4.1, containing 9.5% w/v PEG 3350, 19% w/v PEG 400, 0.19 M magnesium chloride, and 2.5% DMSO, for the reduced form: soaking of the oxidized enzyme crystals in a solution consisting of 0.003 ml of reservoir solution and 0.001 ml of 200 mM DTT for 60 min prior to the first diffraction data collection, 12°C, X-ray diffraction structure determmination and analysis at 1.60-1.83 A resolution, molecular replacement and modelling
purified wild-type homoserine dehydrogenase in apoform, complexed with L-homoserine and NADPH in a closed form, and enzyme mutants K99A and K195A complexed with L-Hse and NADP+, hanging-drop vapour-diffusion method, mixing of 0.002 ml of 5 mg/ml protein in 5 mM Tris-HCl, pH 7.5, and in case of the ligand complex forms 15 mM of each ligand, with 0.002 ml of reservoir solution containing 3.3-4.0 M sodium formate and 50 mM CAPS, pH 10.0, X-ray diffraction structure determination and analysis at 1.83 A, 2.00 A, 1.87 A, and 1.93 A resolution, respectively, molecular replacement method using the TtHSDx02L-Hse structure (PDB ID 5XDF) as the search model
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