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Catalytic Site Atlas Version 2.2.12
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CSA entry for 1jxh
Original Entry
Title:
Transferase
Compound:
Phosphomethylpyrimidine kinase
Mutant:
No
UniProt/Swiss-Prot:
P55882-THID_SALTY
EC Class:
2.7.4.7
Other CSA Entries:
Overview of all sites for 1jxh
Homologues of 1jxh
Entries for UniProt/Swiss-Prot: P55882
Entries for EC: 2.7.4.7
Other Databases:
PDB entry: 1jxh
PDBsum entry: 1jxh
UniProt/Swiss-Prot: P55882
IntEnz entry: 2.7.4.7
Literature Report:
Introduction:
HMPP 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.
Mechanism:
In 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.
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Found by:
Literature reference 

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
LYSA 176 176Sidechain
ElectrostaticTransition state
Acts to stabilise the transition state through electrostatic contacts with the gamma phosphate.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11839308 Current protein Structural similarity to homologue of known mechanism
PubMed ID 11839308 Current protein Conservation of residue
PubMed ID 11839308 Current protein Residue is positioned appropriately (ligand position hypothetical)

ResidueChainNumberUniProt numberFunctional part FunctionTargetDescription
GLYA 210 210Backbone amide
ElectrostaticTransition state
Acts to stabilise the transition state through favourable contacts between the gamma phosphate and the amide group of the residue.
Evidence from paper Evidence concerns Evidence type
PubMed ID 11839308 Current protein Residue is positioned appropriately (ligand position hypothetical)
PubMed ID 11839308 Current protein Conservation of residue
PubMed ID 11839308 Current protein Structural similarity to homologue of known mechanism
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.
References:
1
Crystal structure of 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase from Salmonella typhimurium at 2.3 A resolution.
G. Cheng and E. M. Bennett and T. P. Begley and S. E. Ealick
Structure (Camb) 10, (2) 225-35, (2002).
11839308
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