Enzymes involved in the degradation of aromatic compounds - mechanism, evolution and regulation

参与芳香族化合物降解的酶——机制、进化和调控

• 批准号: 238284-2010
• 负责人: Seah, Stephen
• 金额: $ 2.4万
• 依托单位: University of Guelph
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2013
• 资助国家: 加拿大
• 起止时间: 2013-01-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=524274
• 关键词: Enzymes; involved; degradation; aromatic; compounds

The myriad of chemical reactions occurring within living systems are catalyzed by enzymes. Most enzymes are proteins which fold into a compact three dimensional structures, creating a unique environment where chemical catalysis can occur. Therefore, the structure of an enzyme has a bearing on function. S. Seah and his students are studying this structure-function relationship in enzymes known as pyruvate aldolases, that evolve independently to catalyze similar reactions. Specifically, his team is determining if these aldolases utilize similar chemical strategies for catalysis. They are also studying how some of these aldolases regulate their catalytic activity and interact with other enzymes in a metabolic pathway to ensure efficiency. The aldolases being studied are from aromatic degradation pathways that are useful for bioremediation of toxic aromatic pollutants, such as Polychlorinated biphenyls. Aldolases are also useful for the synthesis of pharmaceutical compounds. One of the aldolase being studied is from bacteria that cause tuberculosis, and therefore this work may lead o the development of new drugs against this disease. At the broader level, learning the principles of how nature creates new enzymes will allow us to apply this knowledge to design new biological catalysts for application in medicine and industry. The research work will also contribute to the new area of "functional genomics" allowing us to predict with greater accuracy the functions of enzymes based on the sequences of their building blocks (amino acids) or 3D fold. Undergraduate, graduate and postdoctoral trainees participating in this work will learn to solve scientific problems using research tools drawn from molecular biology and biochemistry.

在生命系统中发生的无数化学反应都是由酶催化的。 大多数酶是蛋白质，它们折叠成紧凑的三维结构，创造了一个独特的环境，可以发生化学催化。因此，酶的结构与功能有关。 S. Seah和他的学生正在研究称为丙酮酸醛缩酶的酶中的这种结构与功能关系，这些酶独立进化以催化类似的反应。 具体来说，他的团队正在确定这些醛缩酶是否利用类似的化学策略进行催化。 他们还在研究这些醛缩酶如何调节其催化活性，并与代谢途径中的其他酶相互作用，以确保效率。正在研究的醛缩酶来自芳香族降解途径，可用于有毒芳香族污染物（如多氯联苯）的生物修复。 醛缩酶也可用于合成药物化合物。正在研究的一种醛缩酶来自于导致结核病的细菌，因此这项工作可能会导致开发对抗这种疾病的新药。在更广泛的层面上，学习自然界如何创造新酶的原理将使我们能够应用这些知识来设计新的生物催化剂，用于医学和工业。这项研究工作也将有助于“功能基因组学”的新领域，使我们能够更准确地预测酶的功能的基础上，他们的积木（氨基酸）或3D折叠的序列。 参加这项工作的本科生、研究生和博士后学员将学习使用分子生物学和生物化学的研究工具解决科学问题。