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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1hka

E.C. name2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase
SpeciesEscherichia coli (Bacteria)
E.C. Number (IntEnz) 2.7.6.3
CSA Homologues of 1hkaThere are 26 Homologs
CSA Entries With UniProtID P26281
CSA Entries With EC Number 2.7.6.3
PDBe Entry 1hka
PDBSum Entry 1hka
MACiE Entry M0151

Literature Report

Introduction6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase(HPPK) catalyses the transfer of pyrophosphate from ATP to 6-hydroxymethyl-7,8-dihydropterin(HP), the first reaction in the folate biosynthesis.
Folate cofactors are essential for life - they are required for the biosynthesis of purine and pyrimidine bases and certain amino acids. Mammals obtain folate from their diets by an active transport system. In contrast, many microorganisms lack the active transport system and must synthesise folates de novo. Therefore, enzymes in the folate biosynthesis pathway, including HPPK, are target for developing antimicrobial agents.
MechansimThe catalysis follows an inline displacement mechanism. The hydroxyl group of HP performs a nucleophilic attack to the beta-phosphate group of ATP to yield HP-pyrophosphate and AMP. Arg92, Arg82 and two Mg2+ ions stabilise the transition state. Both Mg2+ ions activate the beta-phosphorus for the nucleophilic attack and the Mg2+ ion coordinated to the hydroxyl group of HP reduces the hydroxyl group's pKa to facilitate the reaction.
Reaction

Catalytic Sites for 1hka

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
ArgA9293macie:sideChainIt interacts with the alpha-, beta- or both phosphates of ATP to stabilise the negative charge developed in the transition state.
ArgA8283macie:sideChainIt interacts with the alpha-phosphate of ATP to stabilise the negative charge developed in the transition state.

Literature References

Notes:As in other pyrophosphoryl transfer enzymes, two Mg2+ ions are required for the catalysis by HPPK but there is no number assigned for the two Mg2+ ions in the pdb sequence file.
Li Y
Catalytic roles of arginine residues 82 and 92 of Escherichia coli 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: site-directed mutagenesis and biochemical studies.
Biochemistry 2003 42 1581-1588
PubMed: 12578371
Blaszczyk J
Catalytic center assembly of HPPK as revealed by the crystal structure of a ternary complex at 1.25 A resolution.
Structure 2000 8 1049-1058
PubMed: 11080626
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