Steve Ealick's Research Group


4-Amino-5-hydroxymethyl-2-methylpyrimidine Phosphate Kinase from Salmonella typhimurium


PDB files:

1JXH (native)
1JXI (complexed with 4-amino-5-hydroxymethyl-2-methylpyrimidine)

Description:

4-Amino-5-hydroxymethyl-2-methylpyrimidine phosphate kinase (HMPP kinase aka ThiD) catalyzes two related reactions in consecutive steps of the thiamin phosphate biosynthetic pathway. In the first reaction, HMPP kinase transfers the terminal phosphate of ATP to the hydroxyl group of HMP to form 4-amino-5-hydroxymethyl-2-methylpyrimidine phosphate (HMP-P). This reaction is used to salvage HMP from the growth medium. In the second reaction, HMPP kinase transfers the terminal phosphate from another molecule of ATP to the phosphomethyl group of HMP-P to form HMP-PP, the substrate for thiamin phosphate synthase This reaction is an essential step for the biosynthesis of thiamin pyrophosphate.

The monomers of HMPP kinase are identical subunits of approximately 31 kDa each. Like other members of the ribokinase family, it has a common core structure consisting of a central eight-stranded β-sheet that is flanked by eight structurally conserved αβ-helices; five on one side and three on the other.

 

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HMPP kinase is a homodimer and is in the P41212 space group. Each HMPP kinase monomer possesses one self-contained active site that begins near the dimer interface and extends outward along the C-terminal edge of the central β-sheet. The two active sites in the dimer are separated by approximately 20-25 Å.

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Each active site contains one HMP binding site and one ATP binding site. See the schematic drawing showing the active site. Key hydrogen bonds are shown with dashed lines.

Reference:

Cheng G, Bennett EM, Begley TP and Ealick SE. Crystal Structure of 4-Amino-5-hydroxymethyl-2-methylpyrimidine Phosphate Kinase from Salmonella typhimurium at 2.3 Å Resolution. Structure 10:225-235 (2002).



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