EzCatDB: S00258

DB codeS00258
RLCP classification3.103.78000.1130
CATH domainDomain 13.30.70.560Catalytic domain
E.C.2.7.6.3
CSA1hka


Enzyme Name
Swiss-protKEGG

P26281
Protein name2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase
2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase
H2-pteridine-CH2OH pyrophosphokinase
7,8-dihydroxymethylpterin-pyrophosphokinase
HPPK
7,8-dihydro-6-hydroxymethylpterin pyrophosphokinase
hydroxymethyldihydropteridine pyrophosphokinase
SynonymsEC 2.7.6.3
7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase
HPPK
6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase
PPPK

KEGG pathways
MAP codePathways
MAP00790Folate biosynthesis

Swiss-prot:Accession NumberP26281
Entry nameHPPK_ECOLI
ActivityATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8- dihydropteridine = AMP + (2-amino-4-hydroxy-7,8-dihydropteridin-6- yl)methyl diphosphate.
SubunitMonomer.
Subcellular location
Cofactor


CofactorsSubstratesProducts
KEGG-idC00305C00002C01300C00020C04807
CompoundMagnesiumATP2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridineAMP2-Amino-7,8-dihydro-4-hydroxy-6-(diphosphooxymethyl)pteridine
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotideamide group,amine group,aromatic ring (with nitrogen atoms),carbohydrateamine group,nucleotideamine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ion
1dy3ABound:2x_MGBound:ATPAnalogue:87YUnboundUnbound
1eqmABound:_MGAnalogue:ADPUnboundUnboundUnbound
1eqoABound:2x_MGAnalogue:APCAnalogue:HHPUnboundUnbound
1hkaAUnboundUnboundUnboundUnboundUnbound

Active-site residues
pdbCatalytic residuesCofactor-binding residues
1dy3AARG 84;ARG 92;TYR 116;ARG 121
ASP 95;ASP 97(Mg binding)
1eqmAARG 84;ARG 92;TYR 116;ARG 121
ASP 95;ASP 97(Mg binding)
1eqoAARG 84;ARG 92;TYR 116;ARG 121
ASP 95;ASP 97(Mg binding)
1hkaAARG 84;ARG 92;TYR 116;ARG 121
ASP 95;ASP 97(Mg binding)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[4]Fig.9, p.10552

references
[1]
PubMed ID10080886
JournalJ Mol Biol
Year1999
Volume287
Pages211-9
AuthorsHennig M, Dale GE, D'arcy A, Danel F, Fischer S, Gray CP, Jolidon S, Muller F, Page MG, Pattison P, Oefner C
TitleThe structure and function of the 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Haemophilus influenzae.
[2]
PubMed ID10378268
JournalStructure Fold Des
Year1999
Volume7
Pages489-96
AuthorsXiao B, Shi G, Chen X, Yan H, Ji X
TitleCrystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, a potential target for the development of novel antimicrobial agents.
Related PDB1hka
Related Swiss-protP26281
[3]
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 analogu.
Related PDB1dy3
Related Swiss-protP26281
[4]
PubMed ID11080626
JournalStructure Fold Des
Year2000
Volume8
Pages1049-58
AuthorsBlaszczyk J, Shi G, Yan H, Ji X
TitleCatalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 A resolution.
Related PDB1eqo
[5]
PubMed ID11311059
JournalJ Med Chem
Year2001
Volume44
Pages1364-71
AuthorsShi G, Blaszczyk J, Ji X, Yan H
TitleBisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: synthesis and biochemical and crystallographic studies.
[6]
PubMed ID11546767
JournalJ Biol Chem
Year2001
Volume276
Pages40274-81
AuthorsXiao B, Shi G, Gao J, Blaszczyk J, Liu Q, Ji X, Yan H
TitleUnusual conformational changes in 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as revealed by X-ray crystallography and NMR.
Related PDB1eqm
[7]
PubMed ID11381532
JournalJ Mol Graph Model
Year2001
Volume19
Pages70-7
AuthorsYan H, Blaszczyk J, Xiao B, Shi G, Ji X
TitleStructure and dynamics of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase.
[8]
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.

comments
According to the literature [4], the catalysis of this enzyme proceeds through the transition state with some associative character.
(1) The coordination of the two Mg2+ ions with the transferred phosphate group (beta-phosphate) activates the beta-phosphorus atom for the nucleophilic attack, as well as reduces the pKa of the hydroxyl group of acceptor substrate to facilitate the reaction [4].
(2) The Mg2+ ions also stabilize the negative charge developed in the transition state of the reaction.

createdupdated
2002-08-302010-02-22


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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