DB code: S00258

RLCP classification 3.103.78000.1130 : Transfer
CATH domain 3.30.70.560 : Alpha-Beta Plaits Catalytic domain
E.C. 2.7.6.3
CSA 1hka
M-CSA 1hka
MACiE

CATH domain Related DB codes (homologues)

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P26281 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase
EC 2.7.6.3
7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase
HPPK
6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase
PPPK
NP_414684.1 (Protein)
NC_000913.2 (DNA/RNA sequence)
YP_488445.1 (Protein)
NC_007779.1 (DNA/RNA sequence)
PF01288 (HPPK)
[Graphical View]

KEGG enzyme name
2-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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P26281 HPPK_ECOLI ATP + 2-amino-4-hydroxy-6-hydroxymethyl-7,8- dihydropteridine = AMP + (2-amino-4-hydroxy-7,8-dihydropteridin-6- yl)methyl diphosphate. Monomer.

KEGG Pathways
Map code Pathways E.C.
MAP00790 Folate biosynthesis

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C01300 C00020 C04807
E.C.
Compound Magnesium ATP 2-Amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine AMP 2-Amino-7,8-dihydro-4-hydroxy-6-(diphosphooxymethyl)pteridine
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide amide group,amine group,aromatic ring (with nitrogen atoms),carbohydrate amine group,nucleotide amine group,aromatic ring (with nitrogen atoms),phosphate group/phosphate ion
ChEBI 18420
 18420
 		15422
 15422
 		17083
 44841
 17083
 44841
 		16027
 16027
 		15998
 73083
 15998
 73083
PubChem 888
 888
 		5957
 5957
 		218
 218
 		6083
 6083
 		666
 666
1dy3A Bound:2x_MG Bound:ATP Analogue:87Y Unbound Unbound
1eqmA Bound:_MG Analogue:ADP Unbound Unbound Unbound
1eqoA Bound:2x_MG Analogue:APC Analogue:HHP Unbound Unbound
1hkaA Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1dy3A ARG 84;ARG 92;TYR 116;ARG 121 ASP 95;ASP 97(Mg binding)
1eqmA ARG 84;ARG 92;TYR 116;ARG 121 ASP 95;ASP 97(Mg binding)
1eqoA ARG 84;ARG 92;TYR 116;ARG 121 ASP 95;ASP 97(Mg binding)
1hkaA ARG 84;ARG 92;TYR 116;ARG 121 ASP 95;ASP 97(Mg binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[4]
Fig.9, p.1055 2

References
[1]
Resource
Comments
Medline ID
PubMed ID 10080886
Journal J Mol Biol
Year 1999
Volume 287
Pages 211-9
Authors Hennig M, Dale GE, D'arcy A, Danel F, Fischer S, Gray CP, Jolidon S, Muller F, Page MG, Pattison P, Oefner C
Title The structure and function of the 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase from Haemophilus influenzae.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10378268
Journal Structure Fold Des
Year 1999
Volume 7
Pages 489-96
Authors Xiao B, Shi G, Chen X, Yan H, Ji X
Title Crystal structure of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase, a potential target for the development of novel antimicrobial agents.
Related PDB 1hka
Related UniProtKB P26281
[3]
Resource
Comments
Medline ID
PubMed ID 10452528
Journal FEBS Lett
Year 1999
Volume 456
Pages 49-53
Authors Stammers DK, Achari A, Somers DO, Bryant PK, Rosemond J, Scott DL, Champness JN
Title 2.0 A X-ray structure of the ternary complex of 7,8-dihydro-6-hydroxymethylpterinpyrophosphokinase from Escherichia coli with ATP and a substrate analogu.
Related PDB 1dy3
Related UniProtKB P26281
[4]
Resource
Comments
Medline ID
PubMed ID 11080626
Journal Structure Fold Des
Year 2000
Volume 8
Pages 1049-58
Authors Blaszczyk J, Shi G, Yan H, Ji X
Title Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 A resolution.
Related PDB 1eqo
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 11311059
Journal J Med Chem
Year 2001
Volume 44
Pages 1364-71
Authors Shi G, Blaszczyk J, Ji X, Yan H
Title Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: synthesis and biochemical and crystallographic studies.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 11546767
Journal J Biol Chem
Year 2001
Volume 276
Pages 40274-81
Authors Xiao B, Shi G, Gao J, Blaszczyk J, Liu Q, Ji X, Yan H
Title Unusual conformational changes in 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase as revealed by X-ray crystallography and NMR.
Related PDB 1eqm
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 11381532
Journal J Mol Graph Model
Year 2001
Volume 19
Pages 70-7
Authors Yan H, Blaszczyk J, Xiao B, Shi G, Ji X
Title Structure and dynamics of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 11931659
Journal Biochem J
Year 2002
Volume 363
Pages 313-9
Authors Mouillon JM, Ravanel S, Douce R, Rebeille F
Title Folate synthesis in higher-plant mitochondria: coupling between the dihydropterin pyrophosphokinase and the dihydropteroate synthase activities.
Related PDB
Related UniProtKB

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.

Created Updated
2002-08-30 2010-02-22