title: Thiamin pyrimidine biosynthesis in Candida albicans : a remarkable reaction between histidine and pyridoxal phosphate.
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.
authors.affiliation: Department of Chemistry, Texas A&M University, College Station, 77843, United States.
authors.forename: Rung-Yi
authors.initials: RY
authors.lastname: Lai
authors.forename: Siyu
authors.initials: S
authors.lastname: Huang
authors.forename: Michael K
authors.initials: MK
authors.lastname: Fenwick
authors.forename: Amrita
authors.initials: A
authors.lastname: Hazra
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Kanagalaghatta
authors.initials: K
authors.lastname: Rajashankar
authors.forename: Benjamin
authors.initials: B
authors.lastname: Philmus
authors.forename: Cynthia
authors.initials: C
authors.lastname: Kinsland
authors.forename: Jennie Mansell
authors.initials: JM
authors.lastname: Sanders
authors.forename: Steven E
authors.initials: SE
authors.lastname: Ealick
authors.forename: Tadhg P
authors.initials: TP
authors.lastname: Begley
mesh_terms: D002176:Candida albicans / Q000737:chemistry / Q000378:metabolism*; D006639:Histidine / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D011732:Pyridoxal Phosphate / Q000737:chemistry / Q000378:metabolism*; D011743:Pyrimidines / Q000096:biosynthesis* / Q000737:chemistry; D013831:Thiamine / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D011743:Pyrimidines; D006639:Histidine; D011732:Pyridoxal Phosphate; D013831:Thiamine