2TPS

THIAMIN PHOSPHATE SYNTHASE

Summary for 2TPS

• Entry DOI: 10.2210/pdb2tps/pdb
• Descriptor: PROTEIN (THIAMIN PHOSPHATE SYNTHASE), MAGNESIUM ION, THIAMIN PHOSPHATE, ... (5 entities in total)
• Functional Keywords: thiamin biosynthesis, tim barrel
• Biological source: Bacillus subtilis
• Total number of polymer chains: 2
• Total formula weight: 49716.48

Authors

Chiu, H.-J.,Reddick, J.J.,Begley, T.P.,Ealick, S.E. (deposition date: 1999-03-09, release date: 1999-03-18, Last modification date: 2023-12-27)

Primary citation

Chiu, H.J.,Reddick, J.J.,Begley, T.P.,Ealick, S.E.
Crystal structure of thiamin phosphate synthase from Bacillus subtilis at 1.25 A resolution.
Biochemistry, 38:6460-6470, 1999

PubMed Abstract: The crystal structure of Bacillus subtilis thiamin phosphate synthase complexed with the reaction products thiamin phosphate and pyrophosphate has been determined by multiwavelength anomalous diffraction phasing techniques and refined to 1.25 A resolution. Thiamin phosphate synthase is an alpha/beta protein with a triosephosphate isomerase fold. The active site is in a pocket formed primarily by the loop regions, residues 59-67 (A loop, joining alpha3 and beta2), residues 109-114 (B loop, joining alpha5 and beta4), and residues 151-168 (C loop, joining alpha7 and beta6). The high-resolution structure of thiamin phosphate synthase complexed with its reaction products described here provides a detailed picture of the catalytically important interactions between the enzyme and the substrates. The structure and other mechanistic studies are consistent with a reaction mechanism involving the ionization of 4-amino-2-methyl-5-hydroxymethylpyrimidine pyrophosphate at the active site to give the pyrimidine carbocation. Trapping of the carbocation by the thiazole followed by product dissociation completes the reaction. The ionization step is catalyzed by orienting the C-O bond perpendicular to the plane of the pyrimidine, by hydrogen bonding between the C4' amino group and one of the terminal oxygen atoms of the pyrophosphate, and by extensive hydrogen bonding and electrostatic interactions between the pyrophosphate and the enzyme.

PubMed: 10350464
DOI: 10.1021/bi982903z

Experimental method

X-RAY DIFFRACTION (1.25 Å)