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J Am Chem Soc. 2012 Jun 6;134(22):9157-9. doi: 10.1021/ja302474a. Epub 2012 May 24.

Thiamin pyrimidine biosynthesis in Candida albicans : a remarkable reaction between histidine and pyridoxal phosphate.

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1
Department of Chemistry, Texas A&M University, College Station, 77843, United States.

Abstract

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.

PMID:
22568620
PMCID:
PMC3415583
DOI:
10.1021/ja302474a
[Indexed for MEDLINE]
Free PMC Article
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