Dihydropteroate synthase

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Dihydropteroate synthase (DHPS) catalyzes the condensation of 6-hydroxymethyl-7,8-dihydropteridine pyrophosphate
to para-aminobenzoic acid (PABA) to form 7,8-dihydropteroate. DHPs is a key enzyme in folate synthesis. Folate is necessary for nucleic acid synthesis. DHPS is found in bacteria and not in eukaryotes. Hence, it makes a target to sulfonamide antibiotics. Some DHPS contain a dihydro-6-hydroxymethylpterin pyrophosphokinase domain at their N terminal and are named PPPK-DHPS.

3S structures of dihydropteroate synthase3S structures of dihydropteroate synthase

1ad1 – SaDHPS]] - Staphylococcus aureus
1ajz – EcDHPS – Escherichia coli
1tws, [[3v5o – BaDHPS – Bacillus anthracis
2dqw - TtDHPS – Thermus thermophilus
2vef - SpDHPS – Streptococcus pneumonia
2vp8 – MtDHPS – Mycobacterium tuberculosis
2y5j – BcDHPS – Burkholderia cenocepacia
3tzn – YpDHPS – Yersinia pestis

DHPS binary comlexes

1ad4 – SaDHPS + pterin-pyrophosphate
1aj2 – EcDHPS + dihydro-pterin-methanyl-phosphonophosphate
1eye - MtDHPS + pterin-methyl-phosphate
1tww - BaDHPS + hydroxymethylpterin-diphosphate
1twz - BaDHPS + pterin-methyl-phosphate
1tx0 - BaDHPS + pteroic acid
1tx2, 3h21, 3h22, 3h23, 3h24, 3h26, 3h2a, 3h2c, 3h2e, 3h2f, 3h2m, 3h2n, 3h2o, 4d8z, 4d9p, 4dai, 4db7, 4d8a, 4daf - BaDHPS + inhibitor
2dza - TtDHPS + PABA
2dzb - TtDHPS + hydroxymethylpterin-diphosphate
2veg - SpDHPS + pterin-methyl-phosphate
2y5s - BcDHPS + dihydro-pteroate
3tya - BaDHPS + dihydro-pteroate
3tyc - BaDHPS + amino-hydroxymethyl-dihydro-pteridinone
3tr9 - DHPS + pteroic acid – Coxiella burnetii
3tyu – YpDHPS + pteroic acid

DHPS ternary complexes

1aj0 – EcDHPS + sulfanilamide + amino-methyldiene-dihydro-pteridinone
3tyb - BaDHPS + hydroxybenzoic acid + amino-hydroxymethyl-dihydro-pteridinone
3tyd - BaDHPS + pyrophosphate+ amino-hydroxymethyl-dihydro-pteridinone
3tye - BaDHPS + sulfa derivative + amino-hydroxymethyl-dihydro-pteridinone
3tyz - YpDHPS + pyrophosphate + PABA + amino-hydroxymethyl-dihydro-pteridinone
3tzf - YpDHPS + sulfa derivative + hydroxymethylpterin-diphosphate

Bifunctional 6-hydroxymethyl-7,8-dihydropterin pyrophsphokinase-DHPS

3mcm, 3mcn – FtPPPK-DHPS – Francisella tulerensis
3mco - FtPPPK-DHPS + amino-hydroxymethyl-dihydro-pteridinone + methyladenosine triphosphate
2bmb - PPPK-DHPS + pterin-methyl-phosphate - yeast

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman
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