The overall goal for the project is to study the detailed mechanisms of uronate isomerase and adenosyl- cobyric acid synthetase. Uronate isomerase has been identified as a member of the amidohydrolase superfamily, in which most members catalyze hydrolysis reactions. The reaction of uronate isomerase differs from other family members in that it catalyzes the isomerization of glucuronic and galacturonic acid to fructuronic and tagaturonic acid, respectively. The existence of an isomerase in the amidohydrolase superfamily provides an excellent example of divergent evolution of enzyme function. The modifications to the active site that enables an isomerization reaction in this superfamily are of significant interest. Adenosyl- cobyric acid synthetase (CbiP) catalyzes the sequential amidation of carboxylate groups b, d, e, and g of adenosyl-cobyrinic acid a,c-diamide. The mechanism of CbiP is interesting because it catalyzes chemical reactions at multiple sites within the same substrate. Preliminary data suggest that the amidation of these carboxylate groups is ordered and dissociative. The specific order of amidation and the structural basis for this selectivity will be elucidated. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31GM077102-01
Application #
7062628
Study Section
Special Emphasis Panel (ZRG1-GGG-G (29))
Program Officer
Toliver, Adolphus
Project Start
2006-01-01
Project End
2008-12-31
Budget Start
2006-01-01
Budget End
2006-12-31
Support Year
1
Fiscal Year
2006
Total Cost
$30,632
Indirect Cost
Name
Texas A&M University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
078592789
City
College Station
State
TX
Country
United States
Zip Code
77845
Fresquet, Vicente; Williams, LaKenya; Raushel, Frank M (2007) Partial randomization of the four sequential amidation reactions catalyzed by cobyric acid synthetase with a single point mutation. Biochemistry 46:13983-93
Williams, Lakenya; Fresquet, Vicente; Santander, Patricio J et al. (2007) The multiple amidation reactions catalyzed by Cobyric acid synthetase from Salmonella typhimurium are sequential and dissociative. J Am Chem Soc 129:294-5
Williams, LaKenya; Nguyen, Tinh; Li, Yingchun et al. (2006) Uronate isomerase: a nonhydrolytic member of the amidohydrolase superfamily with an ambivalent requirement for a divalent metal ion. Biochemistry 45:7453-62