Structural highlights
Function
THI5_CANAW Responsible for the formation of the pyrimidine heterocycle in the thiamine biosynthesis pathway. Catalyzes the formation of hydroxymethylpyrimidine phosphate (HMP-P) from histidine and pyridoxal phosphate (PLP). The protein uses PLP and the active site histidine to form HMP-P, generating an inactive enzyme. The enzyme can only undergo a single turnover, which suggests it is a suicide enzyme.[1]
Publication Abstract from PubMed
In Saccharomyces cerevisiae , thiamin pyrimidine is formed from histidine and pyridoxal phosphate (PLP). The origin of all of the pyrimidine atoms has been previously determined using labeling studies and suggests that the pyrimidine is formed using remarkable chemistry that is without chemical or biochemical precedent. Here we report the overexpression of the closely related Candida albicans pyrimidine synthase (THI5p) and the reconstitution and preliminary characterization of the enzymatic activity. A structure of the C. albicans THI5p shows PLP bound at the active site via an imine with Lys62 and His66 in close proximity to the PLP. Our data suggest that His66 of the THI5 protein is the histidine source for pyrimidine formation and that the pyrimidine synthase is a single-turnover enzyme.
Thiamin pyrimidine biosynthesis in Candida albicans : a remarkable reaction between histidine and pyridoxal phosphate.,Lai RY, Huang S, Fenwick MK, Hazra A, Zhang Y, Rajashankar K, Philmus B, Kinsland C, Sanders JM, Ealick SE, Begley TP J Am Chem Soc. 2012 Jun 6;134(22):9157-9. Epub 2012 May 24. PMID:22568620[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lai RY, Huang S, Fenwick MK, Hazra A, Zhang Y, Rajashankar K, Philmus B, Kinsland C, Sanders JM, Ealick SE, Begley TP. Thiamin pyrimidine biosynthesis in Candida albicans : a remarkable reaction between histidine and pyridoxal phosphate. J Am Chem Soc. 2012 Jun 6;134(22):9157-9. Epub 2012 May 24. PMID:22568620 doi:http://dx.doi.org/10.1021/ja302474a
- ↑ Lai RY, Huang S, Fenwick MK, Hazra A, Zhang Y, Rajashankar K, Philmus B, Kinsland C, Sanders JM, Ealick SE, Begley TP. Thiamin pyrimidine biosynthesis in Candida albicans : a remarkable reaction between histidine and pyridoxal phosphate. J Am Chem Soc. 2012 Jun 6;134(22):9157-9. Epub 2012 May 24. PMID:22568620 doi:http://dx.doi.org/10.1021/ja302474a
