Engineering modified ligand binding in enzymes

工程改造酶中的配体结合

• 批准号: 227853-2009
• 负责人: Pelletier, Joelle
• 金额: $ 3.39万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2009
• 资助国家: 加拿大
• 起止时间: 2009-01-01 至 2010-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=425298
• 关键词: Engineering; modified; ligand; binding; enzymes

The complex interplay between amino acids at the active site of enzymes results in high catalytic power and specificity. As a result of this complexity, there remains much to be done in order to extend our knowledge from specific examples to general rules. The benefits of better understanding enzyme catalysis are numerous: in our laboratory, we are gaining a better understanding of enzyme-based drug resistances and we are modifying enzymes for their application to organic synthesis. Our research program combines powerful molecular biological methodologies with computer-assisted protein molecular modelling to explore the fundamentals of enzyme catalysis. We combinatorially mutate active-site amino acids that are involved in substrate binding, creating large libraries of mutated enzymes from which we select the subset of functional ones. We characterize the new enzymes with respect to their kinetics, their structure and their dynamics to correlate active-site structure with function.

在酶的活性位点处氨基酸之间的复杂相互作用导致高催化能力和特异性。由于这种复杂性，为了将我们的知识从具体示例扩展到一般规则，还有很多工作要做。更好地了解酶催化的好处是多方面的：在我们的实验室，我们正在更好地了解基于酶的耐药性，我们正在修改酶，使其应用于有机合成。我们的研究计划将强大的分子生物学方法与计算机辅助蛋白质分子建模相结合，以探索酶催化的基本原理。我们组合突变参与底物结合的活性位点氨基酸，创建大型突变酶库，从中选择功能酶的子集。我们的新酶的动力学，其结构和动力学特征，以关联活性位点的结构与功能。