Looking in New Directions for Origins and Cryptic Mechanisms of Enzyme Catalysis

寻找酶催化起源和神秘机制的新方向

• 批准号: 9892015
• 负责人: JUDITH P KLINMAN
• 金额: $ 79.58万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892015
• 关键词: Address; Area; Biochemical; Biological; Biophysics; Catalysis; Chemicals; Coupling; Enzymes; Event; Hydrogen; Kinetics; Motion; PQQ Cofactor; Pathway interactions; Peptides; Post-Translational Protein Processing; Property; Proteins; Reaction; Resolution; Ribosomes; Structure; Time; Vitamins; cofactor; enzyme activity; enzyme mechanism; novel; protein function; prototype; public health relevance; temporal measurement

 DESCRIPTION (provided by applicant): This project is focused on understanding the physical and mechanistic properties of enzymes that underlie their exquisite function. In recent years, protein motions have been implicated as essential to achieve an extremely rapid catalysis of bond cleavage events. A spatial and temporal resolution of such protein motions is being pursued using enzyme prototypes that catalyze hydrogen and methyl transfer reactions. A description of the hierarchy and range of the requisite protein motions (covering time scales that can differ by ca. 1015 fold) will take place utilizing highly developed kinetic and biophysical probes. A second emerging area in biological catalysis concerns the post-translational modification of peptides that have been synthesized at the ribosome. A combination of structural and biochemical probes is addressing the enigmatic pathway that produces the bacterial cofactor and vitamin, pyrroloquinoline quinone. As the result of a number of recent breakthrough observations, it appears that resolution of this long-standing problem is now within reach.

 描述(由申请者提供)：这个项目的重点是了解酶的物理和机械属性，这些属性是其精致功能的基础。近年来，蛋白质运动被认为是实现极快的键断裂事件催化的关键。这种蛋白质运动的空间和时间分辨率正在使用催化氢和甲基转移反应的酶原型来追求。对必需蛋白质运动的层次和范围的描述(覆盖的时间尺度可能相差约1015倍)将利用高度发达的动力学和生物物理探测器进行。生物催化的第二个新兴领域涉及已在核糖体中合成的多肽的翻译后修饰。一种结构和生化探针的组合正在解决产生细菌辅因子和维生素--吡咯喹啉醌的神秘途径。由于最近一些突破性的观察，这个长期存在的问题现在似乎可以得到解决。