Dynamics-Function Relationships of Glyoxalase I

9600968 Stone本研究的目的是研究酶GlxI中活性位点动力学的功能相关性。 异频NMR弛豫数据将用于计算描述快速（ps-ns）和较慢（-ms）时间尺度上的内部运动的参数。 将游离酶与结合到反应产物和过渡态类似物抑制剂上的酶进行比较，将表明活性位点动力学的变化，这些变化沿着酶催化反应的反应坐标发生。 酶动力学在控制和限制功能动力学中的作用将通过与Glx I催化周转率和配体缔合和解离的速率与毫秒时间尺度动力学相关联来研究。 建议的教育活动包括在印第安纳州大学的正式教学职责以及：（1）本科生生物化学课程开发;（2）研究生水平的分子模拟研讨会;（3）研究生教育的书面理解和表达的科学思想;（4）NMR弛豫和动力学分析的NMR专业人员的实践课程;（5）研究生、本科生和高中生的导师制。 %酶是催化化学反应（提高化学反应速率）的蛋白质分子。 它们参与许多重要的生物化学和工业过程。 该研究将调查酶分子中发生的运动以及这些运动与酶功能之间的关系。 从长远来看，这些研究可能使我们能够设计新的酶或设计分子。 建议的教育活动涉及印第安纳州大学的正式教学职责以及：（1）评估和修改本科生生物化学课程，以提高学生为他们的目标职业做好准备;（2）使用手动和计算机模型构建作为研究生水平的教育辅助工具;（3）发展研究论文的批判性阅读和科学思想的简明扼要的书面陈述的研究生课程：（4）为对研究蛋白质运动感兴趣的科学家编写实用课程;以及（5）指导研究生、本科生和高中生，包括特别关注少数民族学生。 ***

9600968 Stone The goal of the research is investigate the functional relevance of active site dynamics in the enzyme glyoxalase I (Glx I). Heteronuclear NMR relaxation data will be used to calculate parameters describing the internal motions on fast (ps-ns) and slower (-ms) time scales. Comparison of the free enzyme with the enzyme bound to reaction product and to transition state analog inhibitors will indicate the changes in active site dynamics that occur along the reaction coordinate of the enzyme-calatyzed reaction. The role of enzyme dynamics in controlling and limiting functional kinetics will be investigated by correlating the rates of Glx I catalytic turnover and of ligand association and dissociation with the millisecond time scale dynamics. The proposed educational activities involve formal teaching responsibilities at Indiana University as well as: (1) undergraduate biochemistry curriculum development; (2) graduate level molecular modeling workshops; (3) graduate education in written comprehension and expression of scientific ideas; (4) a practical course in NMR relaxation and dynamics analysis for NMR professionals; and (5) mentorship of graduate, undergraduate and high school students. %%% Enzymes are protein molecules that catalyze (increase the rate of) chemical reactions. They are involved in many important biochemical and industrial processes. The proposed research will investigate the motions that occur in enzyme molecules and the relationship between these motions and the function of the enzyme. In the long term such studies may enable us to design new enzymes or to design molecules. The proposed educational activities involve formal teaching responsibilities at Indiana University as well as: (1) assessment and modification of the undergraduate biochemistry curriculum to improve the preparation of students for their target careers; (2) use of manual and computerized model building as graduate level educational aids; (3) developme nt of graduate courses in the critical reading of research articles and the clear, concise written presentation of scientific ideas; (4) composition of a practical course for scientists interested in studying motions in proteins; and (5) mentorship of graduate, undergraduate and high school students including a specific focus on minority students. ***