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（由适用提供）：该项目的重点是了解其独家功能的酶的物理和机械性能。近年来，蛋白质运动已被实施，这对于实现键裂解事件的极快催化至关重要。正在使用催化氢和甲基转移反应的酶原型来追求这种蛋白质运动的空间和暂时分辨率。使用高度发达的动力学和生物物理问题，将对所需蛋白质运动的层次结构和范围进行描述。生物催化的第二个新兴区域涉及在核糖体上合成的辣椒的翻译后修饰。结构和生化问题的结合是解决产生细菌辅助因子和维生素吡咯烷酚喹酮的神秘途径。由于最近进行了许多突破性的观察，看来这一长期存在的问题的解决方案现在已经触及了。