Minority Predoctoral Fellowship Program

少数族裔博士前奖学金计划

• 批准号: 7062628
• 负责人: LAKENYA F WILLIAMS
• 金额: $ 3.06万
• 依托单位: TEXAS A&M UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7062628
• 关键词: Escherichia coli; Salmonella typhimurium; active sites; adenosine; adenosine triphosphate; amidation /deamidation; bacterial proteins; enzyme activity; enzyme mechanism; enzyme structure; enzyme substrate; isomerase; ligase; microorganism metabolism; predoctoral investigator; uronate; vitamin B12

DESCRIPTION (provided by applicant): 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.

描述（由申请人提供）：该项目的总体目标是研究糖醛酸异构酶和腺苷钴酸合成酶的详细机制。糖醛酸异构酶已被鉴定为酰胺水解酶超家族的成员，其中大多数成员催化水解反应。糖醛酸异构酶的反应与其他家族成员的不同之处在于，它分别催化葡萄糖醛酸和半乳糖醛酸异构化为果糖醛和塔糖醛酸。酰胺水解酶超家族中异构酶的存在提供了酶功能发散进化的极好例子。对该超家族中能够发生异构化反应的活性位点的修饰引起了人们的极大兴趣。腺苷钴酸合成酶 (CbiP) 催化腺苷钴酸 a,c-二酰胺的羧酸根 b、d、e 和 g 的连续酰胺化。 CbiP 的机制很有趣，因为它可以催化同一基质内多个位点的化学反应。初步数据表明这些羧酸酯基团的酰胺化是有序且解离的。将阐明酰胺化的具体顺序和这种选择性的结构基础。