Steve Ealick's Research Group
Lai RY, Huang S, Fenwick MK, Hazra AB, Zhang Y, Rajashankar KR, Philmus B, Kinsland C, Sanders JM, Ealick SE, and Begley TP. Thiamin pyrimidine biosynthesis in Candida albicans: a remarkable reaction between histidine and pyridoxal phosphate. J. Am. Chem. Soc. 134:9157−9159. (2012).
In S. cerevisiae the thiamin pyrimidine is formed from histidine and pyridoxal phosphate. The origin of all of the pyrimidine atoms has been 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 C. albicans pyrimidine synthase (THI5p) and the reconstitution and preliminary characterization of the enzymatic activity. A structure of 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.
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