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 amidohydrolasesuperfamily, in which most members catalyze hydrolysis reactions. The reaction of uronate isomerase differsfrom other family members in that it catalyzes the isomerization of glucuronic and galacturonic acid tofructuronic and tagaturonic acid, respectively. The existence of an isomerase in the amidohydrolasesuperfamily provides an excellent example of divergent evolution of enzyme function. The modifications tothe 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 ofadenosyl-cobyrinic acid a,c-diamide. The mechanism of CbiP is intersting because it catalyzes chemicalreactions at multiple sites within the same substrate. Preliminary data suggest that the amidation of thesecarboxylate groups is ordered and dissociative. The specific order of amidation and the structural basis forthis selectivity will be elucidated.
| 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 |
