Structure Function & Biosynthesis of Respiratory Enzymes

结构 功能

• 批准号: 6603829
• 负责人: VICTOR L DAVIDSON
• 金额: $ 29.9万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6603829
• 关键词: amine oxidoreductase; bacteria; bacterial genetics; bacterial proteins; catalyst; chemical kinetics; copper; cytochrome c; electron nuclear double resonance spectroscopy; electron transport; enzyme complex; intermolecular interaction; metalloproteins; methylamines; molecular assembly /self assembly; molecular site; posttranslational modifications; protein biosynthesis; protein purification; protein structure function; quinones; recombinant proteins; respiratory enzyme; semiquinone; site directed mutagenesis; thermodynamics

This research project concerns the study of enzyme reaction mechanisms, protein structure-function relationships, protein-protein interactions, protein biosynthesis, and mechanisms of long range biological electron transfer. The results of these studies are helping us to understand mechanisms by which enzymes catalyze reactions, and the molecular details of biological energy transduction and respiration. The proposed studies focus on the tryptophan tryptophylquinone [TTQ] bearing enzyme, methylamine dehydrogenase [MADH], and the electron transfer complex it forms with the type I copper protein amicyanin, and cytochrome c-551i . The proteins in this project have been crystallized free and in complex, and protocols have been established for altering the proteins by site-directed mutagenesis and analyzing their physical properties and physiological functions. This allows us define specific structure-function relationships. Elucidation of factors which influence the specific protein-protein interactions that are required for efficient interprotein electron transfer is providing insight into the process of protein-protein recognition that is common to a wide range of biologic phenomena. Characterization of the catalytic reaction mechanisms of quinoproteins is allowing us to better understand how enzymes, in general, catalyze reactions. Definition of the mechanisms of long range intermolecular electron transfer will allow us to better understand the fundamental processes of respiration and intermediary metabolism at the molecular level. Description of the mechanism of biosynthesis of MADH and TTQ will be relevant to understanding the mechanisms of biosynthesis of complex redox proteins, as well as mechanisms of protein biosynthesis and posttranslational modification of proteins in general.

本研究计画主要探讨酵素反应机制、蛋白质结构与功能关系、蛋白质间相互作用、蛋白质生物合成及生物电子传递机制。 这些研究的结果有助于我们理解酶催化反应的机制，以及生物能量转导和呼吸的分子细节。 拟议的研究集中在色氨酸甲萘醌[TTQ]轴承酶，甲胺脱氢酶[MADH]，和电子转移复合物，它与I型铜蛋白amicyanin，和细胞色素c-551 i形成。 在这个项目中的蛋白质已经结晶的自由和复杂的，和协议已经建立了改变蛋白质的定点诱变和分析其物理性质和生理功能。 这允许我们定义特定的结构-功能关系。 阐明影响高效蛋白质间电子转移所需的特定蛋白质-蛋白质相互作用的因素，为蛋白质-蛋白质识别过程提供了深入了解，这是广泛的生物现象所共有的。醌蛋白催化反应机制的表征使我们能够更好地了解酶一般如何催化反应。 分子间长程电子转移机制的定义将使我们能够更好地理解呼吸和中间代谢在分子水平上的基本过程。 对MADH和TTQ生物合成机制的描述将有助于理解复杂氧化还原蛋白的生物合成机制，以及蛋白质生物合成和蛋白质翻译后修饰的一般机制。