Information on EC 1.14.11.28 - proline 3-hydroxylase

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The expected taxonomic range for this enzyme is: Bacteria, Eukaryota

EC NUMBER
COMMENTARY hide
1.14.11.28
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RECOMMENDED NAME
GeneOntology No.
proline 3-hydroxylase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
L-proline + 2-oxoglutarate + O2 = cis-3-hydroxy-L-proline + succinate + CO2
show the reaction diagram
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-
-
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SYSTEMATIC NAME
IUBMB Comments
L-proline,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)
Requires iron(II) for activity. Unlike the proline hydroxylases involved in collagen biosynthesis [EC 1.14.11.2 (procollagen-proline dioxygenase) and EC 1.14.11.7 (procollagen-proline 3-dioxygenase)], this enzyme does not require ascorbate for activity although it does increase the activity of the enzyme [2]. The enzyme is specific for L-proline as D-proline, trans-4-hydroxy-L-proline, cis-4-hydroxy-L-proline and 3,4-dehydro-DL-proline are not substrates [2].
CAS REGISTRY NUMBER
COMMENTARY hide
162995-24-6
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
strain TH2; strain TH3
-
-
Manually annotated by BRENDA team
strain TH2
-
-
Manually annotated by BRENDA team
strain TH3
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
strain ATCC 12647
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-
Manually annotated by BRENDA team
strain TH1
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-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
P3H2 can function as a tumour suppressors in breast cancer; P3H3 can function as a tumour suppressors in breast cancer
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3,4-dehydro-L-proline + 2-oxoglutarate + O2
cis-3,4-epoxy-L-proline + succinate + CO2
show the reaction diagram
L-2-azetidinecarboxylic acid + 2-oxoglutarate + O2
cis-3-hydroxyazetidine-L-2-carboxylic acid + succinate + CO2
show the reaction diagram
L-pipecolic acid + 2-oxoglutarate + O2
cis-3-hydroxy-L-pipecolic acid + succinate + CO2
show the reaction diagram
L-proline + 2-oxoglutarate + O2
cis-3-hydroxy-L-proline + succinate + CO2
show the reaction diagram
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
L-proline + 2-oxoglutarate + O2
cis-3-hydroxy-L-proline + succinate + CO2
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2-oxoglutarate
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Citric acid
-
30% inhibition at 5 mM
CoCl2
-
82% inhibition at 0.1 mM, 98% inhibition at 1 mM, 5 mM 2-oxoglutarate, 1 mM ferrous sulfate, 5 mM L-ascorbic acid, 100 mM TES pH 7.5, 30C
CuSO4
-
59% inhibition at 0.1 mM, complete inhibition at 1 mM, 5 mM 2-oxoglutarate, 1 mM ferrous sulfate, 5 mM L-ascorbic acid, 100 mM TES pH 7.5, 30C
Ni2+
-
more than 50% inhibition at 1 mM
ZnSO4
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95% inhibition at 0.1 mM, complete inhibition at 1 mM, 5 mM 2-oxoglutarate, 1 mM ferrous sulfate, 5 mM L-ascorbic acid, 100 mM TES pH 7.5, 30C
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
L-ascorbate
-
2 mM, no further stimulation above 2 mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.047 - 0.11
2-oxoglutarate
8.4
3,4-dehydro-L-proline
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-
2.1
L-2-azetidinecarboxylic acid
-
-
3.8 - 100
L-Pipecolic acid
0.2 - 0.56
L-proline
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.2
L-proline
Streptomyces sp.
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100 mM N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid pH 7.0, 5 mM 2-oxoglutarate, 5 mM L-proline, 5 mM L-ascorbate, 1 mM FeSO4, 35C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.00119
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5 mM 2-oxoglutarate, 1 mM ferrous sulfate, 5 mM L-ascorbic acid, 100 mM TES pH 7.5, 30C
0.00132
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-
0.00149
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-
additional information
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recombinant biotransformation of L-proline to cis-3-hydroxy-L-proline in Escherichia coli cells transformed with a synthetic P3H gene, overview
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 7.9
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assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
28 - 30
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assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
ORGANISM
UNIPROT
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
33150
-
calculated
33570
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calculated
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5.5 - 8.5
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activity remained above 85% after 16 h at 4C
664403
5.5 - 9
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activity remained above 85% after 16 h at 4C
664403
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
30
-
below 30C activity remained above 85% after 30 min at pH 6.0
40
-
below 40C activity remained above 85% after 30 min at pH 6.0
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 chromatographic steps to homogeneity
-
5 chromatographic steps near to homogeneity
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli
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gene P3H, DNA and amino acid sequence determination and analysis, preparation of a synthetic gene encoding proline 3-hydroxylase and cloning and overexpression of proline 3-hydroxylase protein in Escherichia coli strain BL21(DE3) resulting in strain SC16497, biotransformation rates, overview
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EXPRESSION
ORGANISM
UNIPROT
LITERATURE
C-P3H is downregulated in lymphoma. Down-regulation is associated with methylation in the CpG islands and is detected in almost all common types of B-cell lymphoma; C-P4H is downregulated in lymphoma. Down-regulation is associated with methylation in the CpG islands and is detected in almost all common types of B-cell lymphoma
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the enzyme expression of P3H2 and P3H3 is downregulated in breast cancer by abberrant CpG methylation in the 5'-regulatory sequences of each gene, methylation of P3H3 is not associated with higher tumour grade and Nottingham prognostic index; the enzyme expression of P3H2 is downregulated in breast cancer by abberrant CpG methylation in the 5'-regulatory sequences of each gene, methylation of P3H2 is specific for breast cancer and does not occur in other cancer cell types, it is strongly associated with higher tumour grade and Nottingham prognostic index
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
G508V
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mutation is associated with high myopia in human. Mutant G508V expressed in insect cells is completely inactive
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pharmacology
the prolyl 3-hydroxylase P3H2 is a novel targets for epigenetic silencing in breast cancer; the prolyl 3-hydroxylase P3H3 is a novel targets for epigenetic silencing in breast cancer