EzCatDB: S00192

DB codeS00192
CATH domainDomain 13.20.20.20Catalytic domain
E.C.2.5.1.15
CSA1aj0


Enzyme Name
Swiss-protKEGG

P0AC13O05701P0A578
Protein nameDihydropteroate synthaseDihydropteroate synthaseDihydropteroate synthase 1dihydropteroate synthase
dihydropteroate pyrophosphorylase
DHPS
7,8-dihydropteroate synthase
7,8-dihydropteroate synthetase
7,8-dihydropteroic acid synthetase
dihydropteroate synthetase
dihydropteroic synthetase
2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine-diphosphate:4-aminobenzoate2-amino-4-hydroxydihydropteridine-6-methenyltransferase
SynonymsDHPS
EC 2.5.1.15
Dihydropteroate pyrophosphorylase
DHPS
EC 2.5.1.15
Dihydropteroate pyrophosphorylase
DHPS 1
EC 2.5.1.15
Dihydropteroate pyrophosphorylase 1

KEGG pathways
MAP codePathways
MAP00790Folate biosynthesis

Swiss-prot:Accession NumberP0AC13O05701P0A578
Entry nameDHPS_ECOLIDHPS_STAAUDHPS1_MYCTU
Activity(2-amino-4-hydroxy-7,8-dihydropteridin-6- yl)methyl diphosphate + 4-aminobenzoate = diphosphate + dihydropteroate.(2-amino-4-hydroxy-7,8-dihydropteridin-6- yl)methyl diphosphate + 4-aminobenzoate = diphosphate + dihydropteroate.(2-amino-4-hydroxy-7,8-dihydropteridin-6- yl)methyl diphosphate + 4-aminobenzoate = diphosphate + dihydropteroate.
SubunitHomodimer.Homodimer.Homodimer (By similarity).
Subcellular location


Cofactor




CofactorsSubstratesProductsintermediates
KEGG-idC00034C04807C00568C00013C00921
CompoundManganese2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine diphosphate4-AminobenzoatePyrophosphateDihydropteroate
Typeheavy metalamine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ionamine group,aromatic ring (only carbon atom),carboxyl groupphosphate group/phosphate ionamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carboxyl group
1ad1AUnboundUnboundUnboundUnboundUnboundUnbound
1ad1BUnboundUnboundUnboundUnboundUnboundUnbound
1ad4ABound:_MNAnalogue:HH2UnboundUnboundUnboundUnbound
1ad4BUnboundUnboundUnboundUnboundUnboundUnbound
1aj0AUnboundAnalogue:PH2Analogue:SANAnalogue:SO4UnboundUnbound
1aj2AUnboundBound:2PHUnboundUnboundUnboundUnbound
1ajzAUnboundUnboundUnboundAnalogue:SO4 283UnboundUnbound
1eyeAAnalogue:_MGUnboundUnboundUnboundUnboundTransition-state-analogue:PMM

Active-site residues
resource
literature [8]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysiscomment
1ad1AASN 11;ASP 19;ARG 52;LYS 203;ARG 239;HIS 241
ASN 11(Manganese binding)
THR 51

1ad1BASN 11;      ;      ;LYS 203;ARG 239;HIS 241
ASN 11(Manganese binding)
THR 51
invisible 15-24, 52-56
1ad4AASN 11;      ;ARG 52;LYS 203;ARG 239;HIS 241
ASN 11(Manganese binding)
THR 51
invisible 13-24
1ad4BASN 11;      ;      ;LYS 203;ARG 239;HIS 241
ASN 11(Manganese binding)
      
invisible 14-24, 50-56
1aj0AASN 22;ASP 30;ARG 63;LYS 221;ARG 255;HIS 257
ASN 22(Manganese binding)
THR 62

1aj2AASN 22;ASP 30;ARG 63;LYS 221;ARG 255;HIS 257
ASN 22(Manganese binding)
THR 62

1ajzAASN 22;ASP 30;ARG 63;LYS 221;ARG 255;HIS 257
ASN 22(Manganese binding)
THR 62

1eyeAASN 13;ASP 21;      ;LYS 213;ARG 253;HIS 255
ASN 13(Manganese binding)
      
invisible 51-64

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]p.27-28
[4]

[8]p.1203-1205, Fig.6

references
[1]
PubMed ID8397083
JournalEur J Biochem
Year1993
Volume216
Pages449-58
AuthorsVolpe F, Ballantine SP, Delves CJ
TitleThe multifunctional folic acid synthesis fas gene of Pneumocystis carinii encodes dihydroneopterin aldolase, hydroxymethyldihydropterin pyrophosphokinase and dihydropteroate synthase
[2]
PubMed ID9118956
JournalEMBO J
Year1997
Volume16
Pages947-57
AuthorsRebeille F, Macherel D, Mouillon JM, Garin J, Douce R
TitleFolate biosynthesis in higher plants: purification and molecular cloning of a bifunctional 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase/7,8-dihydropteroate synthase localized in mitochondria
[3]
CommentsSEQUENCE FROM NUCLEIC ACID, AND X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)
Medline ID97293085
PubMed ID9149138
JournalJ Mol Biol
Year1997
Volume268
Pages21-30
AuthorsHampele IC, D'Arcy A, Dale GE, Kostrewa D, Nielsen J, Oefner C, Page MG, Schonfeld HJ, Stuber D, Then RL
TitleStructure and function of the dihydropteroate synthase from Staphylococcus aureus
Related PDB1ad1,1ad4
Related Swiss-protO05701
[4]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS)
Medline ID97331326
PubMed ID9187658
JournalNat Struct Biol
Year1997
Volume4
Pages490-7
AuthorsAchari A, Somers DO, Champness JN, Bryant PK, Rosemond J, Stammers DK
TitleCrystal structure of the anti-bacterial sulfonamide drug target dihydropteroate synthase
Related PDB1aj0,1aj2,1ajz
Related Swiss-protP0AC13
[5]
PubMed ID10329458
JournalBiochem Biophys Res Commun
Year1999
Volume258
Pages752-7
AuthorsVinnicombe HG, Derrick JP
TitleDihydropteroate synthase from Streptococcus pneumoniae: characterization of substrate binding order and sulfonamide inhibition
[6]
PubMed ID10452528
JournalFEBS Lett
Year1999
Volume456
Pages49-53
AuthorsStammers DK, Achari A, Somers DO, Bryant PK, Rosemond J, Scott DL, Champness JN
Title2.0 A X-ray structure of the ternary complex of 7,8-dihydro-6-hydroxymethylpterinpyrophosphokinase from Escherichia coli with ATP and a substrate analogue
[7]
PubMed ID11076529
JournalBiochemistry
Year2000
Volume39
Pages13880-90
AuthorsSmith AE, Matthews RG
TitleProtonation state of methyltetrahydrofolate in a binary complex with cobalamin-dependent methionine synthase
[8]
CommentsErratum in: J Mol Biol 2000 Nov 10;303(5):843
PubMed ID11007651
JournalJ Mol Biol
Year2000
Volume302
Pages1193-212
AuthorsBaca AM, Sirawaraporn R, Turley S, Sirawaraporn W, Hol WG
TitleCrystal structure of Mycobacterium tuberculosis 7,8-dihydropteroate synthase in complex with pterin monophosphate: new insight into the enzymatic mechanism and sulfa-drug action
Related PDB1eye
[9]
PubMed ID11426433
JournalTrends Parasitol
Year2001
Volume17
Pages265-6
AuthorsHyde JE, Sims PF
TitleSulfa-drug resistance in Plasmodium falciparum
[10]
PubMed ID11931659
JournalBiochem J
Year2002
Volume363
Pages313-9
AuthorsMouillon JM, Ravanel S, Douce R, Rebeille F
TitleFolate synthesis in higher-plant mitochondria: coupling between the dihydropterin pyrophosphokinase and the dihydropteroate synthase activities
[11]
PubMed ID12039964
JournalJ Biol Chem
Year2002
Volume277
Pages28841-7
AuthorsIllarionova V, Eisenreich W, Fischer M, Haussmann C, Romisch W, Richter G, Bacher A
TitleBiosynthesis of tetrahydrofolate. Stereochemistry of dihydroneopterin aldolase

comments
Although the detailed catalytic mechanism has not been elucidated for this enzyme, the following information on catalytic residues are available, according to the literature [8]:
(a) Asp30 (of 1aj0) on the flexible loop-1 may act as a general acid to protonate the leaving phoshpate oxygen.
(b) Asn22, Arg63, Arg255, and His257 seem to stabilize the leaving phosphate group, along with the bound manganese, and the mainchain amide of Thr62.
(c) The positive charges on the sidechains from Lys221 and Arg255 might give an electron-withdrawing effect on the pyrazine ring of the substrate H2PtPP (C04807), so that the incoming amino group of the second substrate pABA (C00568) could attack on the C9 atom of H2PtPP.

createdupdated
2004-03-222009-03-17


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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