PROTON TUNNELING IN ENZYME REACTIONS

酶反应中的质子隧道

• 批准号: 3467930
• 负责人: CHRISTOPHER J.L. MURRAY
• 金额: $ 11.38万
• 依托单位: UNIVERSITY OF ARKANSAS AT FAYETTEVILLE
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3467930
• 关键词: carbon; chemical bond resonance; chemical reaction; computer program /software; deuterium; dihydroxyacetone; enzyme mechanism; enzyme structure; hydrogen transport; nonradiation isotope effect; protein engineering; quantum chemistry; radionuclides; radiotracer; site directed mutagenesis; triose phosphate isomerase; tritium

Quantum effects in biological hydrogen transfers will be characterized using a newly-developed technique of multiple isotopic labeling to measure a breakdown in the semi-classical Swain-classical Swain-Schaad relation. The proton transfers catalyzed by triosephosphate isomerase (TIM) have been well characterized and provide a unique system with which to examine proton tunneling and coupled proton motion in enzyme reactions. Primary and secondary hydrogen kinetic isotope effects will be measured for the TIM reaction and the corresponding non-enzyme-catalyzed reactions. The effect of changing the barrier width and orientation of the active-site acid=base catalysts on proton tunneling will be examined using the techniques of site-directed mutagenesis. The program BEBOVIB-IV will be used to perform a normal mode analysis of model reactants, products, and transition-state structures from which reaction-coordinate frequencies and isotope effects will be modeled. Tests of current ideas and models regarding enzyme catalysis include answering questions as to how reaction-coordinate proton motions are coupled to the motion of non-transferred protons and to the vibrational motions of proteins, how reaction-coordinate frequencies vary for enzyme and non-enzyme-catalyzed reactions, and whether enzymes lower the intrinsic barriers for proton transfer to and from carbon.

生物氢转移中的量子效应将被表征