Compounds containing reduced forms of phosphorus (i.e. P(III) or P(I)) are widespread in Nature. Despite this, few studies have been reported detailing investigations of enzymes that catalyze phosphorus redox chemistry. In this program, we are interested in the mechanisms of catalysis of two such proteins, phosphite dehydrogenase (PtxD) and hypophosphite dioxygenase (HtxA). These enzymes perform entirely unprecedented reactions and will be studied to gain a better understanding of their catalytic mechanisms as well as their evolutionary origin. In addition, we have shown that phosphite dehydrogenase is a versatile cofactor regeneration enzyme, and a better understanding of catalysis may allow improvements in catalytic efficiency. The studies in this grant focus on the associative vs. dissociative character of the oxidation of phosphite to phosphate by PtxD. To this end, investigations with alternative substrates and site directed mutants will be conducted, and a major focus will be devoted to obtaining crystallographic characterization. The studies on HtxA focus on potential use of alternative substrates as well as developing a fundamental understanding of the mode of catalysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM063003-04
Application #
7087678
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Preusch, Peter C
Project Start
2003-07-01
Project End
2007-06-30
Budget Start
2006-07-01
Budget End
2007-06-30
Support Year
4
Fiscal Year
2006
Total Cost
$216,071
Indirect Cost
Name
University of Illinois Urbana-Champaign
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
041544081
City
Champaign
State
IL
Country
United States
Zip Code
61820
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Whitteck, John T; Ni, Weijuan; Griffin, Benjamin M et al. (2007) Reassignment of the structure of the antibiotic A53868 reveals an unusual amino dehydrophosphonic acid. Angew Chem Int Ed Engl 46:9089-92
Woodyer, Ryan D; Li, Gongyong; Zhao, Huimin et al. (2007) New insight into the mechanism of methyl transfer during the biosynthesis of fosfomycin. Chem Commun (Camb) :359-61
van der Donk, Wilfred A (2006) Rings, radicals, and regeneration: the early years of a bioorganic laboratory. J Org Chem 71:9561-71
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