Hydrogen Tunneling in Enzyme Reactions

酶反应中的氢隧道

• 批准号: 9816791
• 负责人: Judith Klinman
• 金额: $ 39.5万
• 依托单位: University of California-Berkeley
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-03-01 至 2002-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9816791&HistoricalAwards=false
• 关键词: Hydrogen; Tunneling; Enzyme; Reactions

9816791Dr. Klinman's work has been focused in two directions: expansion of the data base of proteins that utilize quantum mechanical behavior to accelerate the cleavage of C-H bonds and understanding the role of protein structure in this process. Increasingly the data point toward a revised view of enzyme catalysis in which we must move beyond a "classic" view of enzyme active sites. Such a "classic" picture depicts the protein catalyst as a "scaffold" for the presentation of multiple functional groups (cofactors, metals, amino acid side chains) to substrate; these groups then participate in a reduction in the height of the free energy barrier for the bond rearrangement steps. This picture must now be revised to include a role for proteins in modulating barrier width, as well as height, i.e.; the entire barrier shape is subject to modification as a means of providing rate acceleration. A second feature of "classic" catalysis is treatment of the enzymatic reaction barrier as a static entity. Increasingly there is evidence that a role for protein dynamical modes must be incorporated in modulating reaction barrier shapes and, hence, catalytic rate accelerations.Studies of the relationship between protein structure and function are fundamental to future advances in modern biochemistry and molecular biology. For example, use of mutagenesis to alter enzyme specificity and efficiency requires detailed understanding of the underlying paradigms for catalysis. The chemical industry has also begun to benefit from the emergence of designed catalysts which have the potential to expand reaction types and stereoselectivities beyond those found in naturally existing protein catalysts. Principles learned from studies of protein structure and function are directly applicable to the de novo design of biomemetic systems.

9816791dr。克林曼的工作集中在两个方向上：利用量子机械行为来加速C-H键的裂解并了解蛋白质结构在此过程中的作用的蛋白质数据库的扩展。 越来越多的数据指向了对酶催化的修订视图，我们必须超越酶活性位点的“经典”视图。 这样的“经典”图片将蛋白质催化剂描述为用于呈现多个官能团（辅助因子，金属，氨基酸侧链）的“支架”。 然后，这些组参与了键重排步的自由能屏障高度的降低。 现在，必须对此图片进行修订，以在调节屏障宽度和高度（即，即）中包括蛋白质的作用； 整个屏障形状会经过修改，作为提供速率加速度的一种手段。 “经典”催化的第二个特征是将酶促反应屏障作为静态实体进行处理。 越来越多的证据表明，蛋白质动力学模式的作用必须在调节反应屏障形状和催化速率加速度中纳入。蛋白质结构与功能之间关系的研究对于现代生物化学和分子生物学的未来进步至关重要。 例如，使用诱变来改变酶的特异性和效率，需要详细了解催化的潜在范例。 化学工业还开始受益于设计的催化剂的出现，这些催化剂有可能扩大反应类型和立体选择性，而不是自然存在的蛋白质催化剂中的反应类型和立体选择性。 从蛋白质结构和功能的研究中学到的原理直接适用于生物计算系统的从头设计。