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（由申请人提供）：该项目的重点是了解酶的物理和机械特性，这些特性是其精致功能的基础。近年来，蛋白质运动被认为对于实现极快速的键断裂事件催化至关重要。人们正在利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时间分辨率。将利用高度发达的动力学和生物物理探针来描述所需蛋白质运动的层次结构和范围（涵盖可能相差约 1015 倍的时间尺度）。生物催化的第二个新兴领域涉及核糖体合成的肽的翻译后修饰。结构和生化探针的结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。由于最近一系列突破性观察的结果，解决这个长期存在的问题似乎已经指日可待。