BINDING ENERGY TRANSDUCTION IN ENZYMATIC CATALYSIS

酶催化中的结合能转换

• 批准号: 3306575
• 负责人: Harvey F. Fisher
• 金额: $ 14.27万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-02-01 至 1995-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3306575
• 关键词: NAD(H) phosphate; alcohol dehydrogenase; biological signal transduction; calorimetry; chemical binding; enzyme complex; enzyme mechanism; enzyme model; glutamate dehydrogenase; nicotinamide adenine dinucleotide; protein denaturation; protein structure function; temperature; thermodynamics

The idea that enzyme-ligand-binding energy can be utilized to drive catalytic steps is a widely held concept, but one that has not been susceptible to direct experimental testing. We have discovered a highly ethalpic two-state macroscopic transition in glutamate dehydrogenase and its complexes which appears to be responsible for the appearance of large deltaCp's. We have developed a unified model which explains a variety of thermodynamic phenomena of pyridine- nucleotide dehydrogenases. On this basis, we now have extended that model to account for free energy transduction in enzymatic catalysis. In more recent work we have found that rather than a single ligand binding induced transition, each enzyme form contains two such transitions, each affected by a given set of ligands. The two transitions are coupled to each other in a complex fashion and their energetics are tightly coupled to that of the thermal unfolding of the protein. Using newly available technology, we hope to obtain definitive evidence for the existence, nature, and scope of occurrence of such transitions, discover the precise manner of their coupling, and explore their possible function as components of the energy transduction machinery of enzymes.

可以利用酶 - 配体结合能来驱动的想法 催化步骤是一个广泛持有的概念，但没有 容易受到直接实验测试。 我们发现了一个 高度伦理学的两态宏观过渡 脱氢酶及其复合物似乎是造成的 大型Deltacp的外观。 我们已经开发了一个统一的模型 这解释了吡啶的多种热力学现象 核苷酸脱氢酶。 在此基础上，我们现在扩展了 解释酶促催化中自由能转导的模型。 在最近的工作中，我们发现不是一个配体 结合诱导的过渡，每种酶形式都包含两个这样的 过渡，每种都受一组配体的影响。 两个 过渡以复杂的方式相互耦合 能量学紧密耦合到热折叠的热量 蛋白质。 使用新的技术，我们希望获得 证明存在，自然和范围的确定证据 发生这种过渡的发生，发现其精确的方式 耦合，并探索它们作为组件的可能功能 酶的能量转导机械。