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2.5.1.15: dihydropteroate synthase

This is an abbreviated version!
For detailed information about dihydropteroate synthase, go to the full flat file.

Word Map on EC 2.5.1.15

Reaction

(7,8-dihydropterin-6-yl)methyl diphosphate
+
4-Aminobenzoate
=
diphosphate
 +
7,8-dihydropteroate

Synonyms

6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase-dihydropteroate synthase, 6-hydroxymethyl-7,8-dihydropterin-pyrophosphokinase-dihydropteroate synthase, 6-hydroxymethyl-7,8-dihydropteroate synthase, 7,8-dihydropteroate synthase, 7,8-dihydropteroate synthetase, 7,8-dihydropteroic acid synthetase, BCG3672c, DHP synthase, DHPS, DHPS-HPPK, DHPS/DHPR, dihydroneopterin aldolase-dihydropterin pyrophosphokinase-dihydropteroate synthase, dihydropteroate diphosphorylase, dihydropteroate synthase, dihydropteroate synthase/hydroxymethyldihydropterin pyrophosphokinase, dihydropteroate synthetase, dihydropteroic synthetase, FolP, folP1, folP2, HPPK-DHPS, hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase, MbDHPS, MtDHPS, Mycobacterium tuberculosis dihydropteroate synthase, PfDHPS, pfPPK-DHPS, PPPK-DHPS, putative dihydropteroate synthase ortholog, pvdhps, PvHPPK-DHPS, PVX_123230, Rv1207, synthase, dihydropteroate

ECTree

     2 Transferases
         2.5 Transferring alkyl or aryl groups, other than methyl groups
             2.5.1 Transferring alkyl or aryl groups, other than methyl groups (only sub-subclass identified to date)
                2.5.1.15 dihydropteroate synthase

Engineering

Engineering on EC 2.5.1.15 - dihydropteroate synthase

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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D96N
-
mutation improves phage display efficiency of the enzyme
D96N/C137I/C172M/C242A
-
130fold improvement in phage display efficiency compared to wild-type enzyme
G58A
site-directed mutagenesis, cannot replace DHPR in Escherichia coli, affects the binding affinity for FMN
K31A
site-directed mutagenesis, can replace DHPR in Escherichia coli, affects the binding affinity for FMN
K51A
site-directed mutagenesis, can replace DHPR in Escherichia coli, affects the binding affinity for FMN
K92E
site-directed mutagenesis, can replace DHPR in Escherichia coli, affects the binding affinity for FMN
M28E
site-directed mutagenesis, can replace DHPR in Escherichia coli, affects the binding affinity for FMN
P55A
mutation associated with dapsone resistance
P55L
mutation associated with dapsone resistance
T53A
mutation associated with dapsone resistance
T53I
mutation associated with dapsone resistance
T53V
mutation associated with dapsone resistance
A437G
A437G/A581G
-
mutant enzyme is resistant against inhibition by sulfadoxine, sulfpyridine, sulfadimethoxine, sulfamethoxazole, sulfaquinoxaline and sulfisoxazole (inhibitors of wild-type enzyme)
A437G/K540E
A581G
the mutation strongly decreases the catalytic efficiency (kcat/Km) of the enzyme with 4-aminobenzoate as substrate
A613S
A613T
the mutation slightly decreases the catalytic efficiency (kcat/Km) of the enzyme with 4-aminobenzoate as substrate
DELTA247-306
-
deletion of the parasite-specific insertion: Km values for (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoate are increased compared to mutant DELTA257-306 but still decreased compared to wild type, catalytic efficacy (kcat) is comparable to wild type
DELTA257-306
-
deletion of the parasite-specific insertion: Km values for (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoate are significantly decreased compared to wild type, catalytic efficacy (kcat) is at least 2fold decreased compared to wild type
DELTA74-80
-
deletion of the parasite-specific insertion: Km values for (2-amino-4-hydroxy-7,8-dihydropteridin-6-yl)methyl diphosphate and p-aminobenzoate are 2 to 3 fold higher compared to wild type, catalytic efficacy (kcat) is at least 2fold decreased compared to wild type
DELTA74-86
-
no DHPS activity is detected
K540E
K540N
-
parasites collected during October 2005 have mutations associated with a lower level of pyrimethamine resistance and a higher level of sulfadoxine resistance, as well as a novel K540N mutation in PfDHPS gene. The emergence of this parasite population coincides with the widespread use of an additional antifolate drug, trimethoprim-sulfamethoxazole, to treat other infections during January-March 2005
S436A
little association with between mutantion and sulfa drug resistance in patients
S436A/A437G
the mutations increase the catalytic efficiency (kcat/Km) of the enzyme by 1.6fold with 4-aminobenzoate as substrate
S436F/A437G/A613S
S436F/A437G/A613T
S436F/A613S
the mutations strongly decrease the catalytic efficiency (kcat/Km) of the enzyme with 4-aminobenzoate as substrate
S436F/A613T
the mutations strongly decrease the catalytic efficiency (kcat/Km) of the enzyme with 4-aminobenzoate as substrate
A383G
A383G/A553G
-
mutation does not much influence the enzyme catalytic activity. Mutant becomes 13fold more resistant to sulfadoxine than the wild type
A553G
D459A
high prevalence amino acid mutation observed in Hormozgan Province, southern Iran. The high prevalence of point mutation of Pvdhps genotype necessitates change in programmes and guidelines to eliminate Plasmodium vivax in future
K512D
K512E
S382A
S382A/A383G/A553G
-
mutation does not much influence the enzyme catalytic activity. Mutant becomes 13fold more resistant to sulfadoxine than the wild type
V585A
A383G
S382A
V585A
-
drug resistance mutation. Resistance mutations subtly alters the intricate enzyme/4-aminobenzoate/sulfadoxine interactions such that DHPS affinity for 4-aminobenzoate is diminished only moderately, but its affinity for sulfadoxine is changed substantially
-
A383G
S382A
V585A
-
drug resistance mutation. Resistance mutations subtly alters the intricate enzyme/4-aminobenzoate/sulfadoxine interactions such that DHPS affinity for 4-aminobenzoate is diminished only moderately, but its affinity for sulfadoxine is changed substantially
-
P519S
mutant with implicated sulfa drug resistance
P57S
-
the prevalence of DHPS mutations in Pneumocystis jirovecii strains isolated from South African Pneumocystis jirovecii pneumonia patients are examined. Mutations resulting in amino-acid substitutions Thr55Ala and/or Pro57Ser are detected in Pneumocystis jirovecii from 85/151 (56%) patients. The high frequency of PCP episodes with Pneumocystis jirovecii harbouring DHPS mutations in South Africa indicates that populations of this fungus are evolving under considerable selective pressure exerted by sulfa-containing antibiotics
T517A
mutant with implicated sulfa drug resistance
T55A
-
the prevalence of DHPS mutations in Pneumocystis jirovecii strains isolated from South African Pneumocystis jirovecii pneumonia patients are examined. Mutations resulting in amino-acid substitutions Thr55Ala and/or Pro57Ser are detected in Pneumocystis jirovecii from 85/151 (56%) patients. The high frequency of PCP episodes with Pneumocystis jirovecii harbouring DHPS mutations in South Africa indicates that populations of this fungus are evolving under considerable selective pressure exerted by sulfa-containing antibiotics
P559S
mutant with implicated sulfa drug resistance
T557A
mutant with implicated sulfa drug resistance
T557A/P559S
mutant with implicated sulfa drug resistance
T557V/P559S
mutant with implicated sulfa drug resistance
T597V/P599S
-
the mutant has very low p-aminobenzoic acid dependence, short generation time and and high sulfamethoxazole resistance. Upregulated p-aminobenzoic acid synthesis is implicated as a mechanism for sulfa drug resistance
E208K
mutation restores trimethoprim susceptibility closer to wild-type levels while further increasing sulfonamide resistance
F17L
mutation directly lead to sulfonamide resistance while increasing susceptibility to trimethoprim
S18L
mutation directly lead to sulfonamide resistance while increasing susceptibility to trimethoprim
T51M
mutation directly lead to sulfonamide resistance while increasing susceptibility to trimethoprim
GS60
insertion of glycine-serine dipeptide into loop 2 beginning at position 60, sulfonamide resistant, no effect on diphosphate affinity, no effect on 6-hydroxymethyl-7,8-dihydropterin diphosphate binding: KD: 46 +/-5 microM (k(on): 260000 1/M*s, k(off): 12 1/s), reduced binding of p-aminobenzoic acid: KD: 16 +/-6 microM, no detectable binding of sulfamethoxazole
InsY63
insertion of tyrosine residue in loop 2, sulfonamide resistant, no effect on diphosphate affinity, no effect on 6-hydroxymethyl-7,8-dihydropterin diphosphate binding: KD: 48 +/-5 microM (k(on) = 240000 1/M*s, k(off): 11 1/sec), reduced binding of p-aminobenzoic acid: KD: 50 +/-6 microM, no detectable binding of sulfamethoxazole
additional information