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Search The CSA
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Catalytic Site Atlas

CSA LITERATURE entry for 1jxh

E.C. namehydroxymethylpyrimidine kinase
SpeciesSalmonella typhimurium (Bacteria)
E.C. Number (IntEnz) 2.7.1.49
CSA Homologues of 1jxhThere are 29 Homologs
CSA Entries With UniProtID P55882
CSA Entries With EC Number 2.7.1.49
PDBe Entry 1jxh
PDBSum Entry 1jxh
MACiE Entry 1jxh

Literature Report

IntroductionHMPP kinase is a key enzyme in the biosynthetic pathway for the formation of thiamine. The bacterial form of the enzyme described here is a member of the ribokinase/sugar kinase family, meaning that it displays significant sequence and structural homology with a large number of kinases with different substrates such as Adenosine kinase. It is unusual however because it is able to catalyse two consecutive steps in the synthesis of thiamine; phosphorylation of 4-amino-5-hydroxymethyl-5-methyl pyrimidine (HM) to give HMP followed by phosphorylation of HMP to give HMPP. This makes studying the enzyme interesting for understanding the specificity of the active site.
MechansimIn common with the other members of the ribokinase family, HMPP kinase catalyses an SN2 type in line displacement reaction where the substrate acts as the nucleophile to attack the gamma phosphate of ATP, forming a pentavalent phosphate transition state. This is stabilised by Mg2+, Gly 210 and Lys 176 at the active site, and collapses to release the end products.
Reaction

Catalytic Sites for 1jxh

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyA210210macie:mainChainAmideActs to stabilise the transition state through favourable contacts between the gamma phosphate and the amide group of the residue.
LysA176176macie:sideChainActs to stabilise the transition state through electrostatic contacts with the gamma phosphate.

Annotated By Reference To The Literature - Site 2 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
GlyB210210macie:mainChainAmideActs to stabilise the transition state through favourable contacts between the gamma phosphate and the amide group of the residue.
LysB176176macie:sideChainActs to stabilise the transition state through electrostatic contacts with the gamma phosphate.

Literature References

Notes:Mg2+ is not present in the crystal structure, however by analogy to the other members of the sugar kinase superfamily it is expected to be present and to have a catalytic role in stabilisation of the pentavalent phosphate transition state.
Cheng G
Crystal structure of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase from Salmonella typhimurium at 2.3 A resolution.
Structure 2002 10 225-235
PubMed: 11839308
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