CHEMISTRY AND BIOCHEMISTRY OF ENERGY TRANSFER

能量转移的化学和生物化学

基本信息

批准号：
2608743
负责人：
WILLIAM P JENCKS
金额：
$ 18.72万
依托单位：
BRANDEIS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1978
资助国家：
美国
起止时间：
1978-12-01 至 1999-11-30
项目状态：
已结题

项目摘要

Mechanisms of group transfer reactions and their catalysis will be studied in enzymic and nonenzymic systems and mechanisms for the conversion of chemical energy into work will be examined with the calcium-transporting ATPase of sarcoplasmic reticulum. This subject is important in the control and function of healthy and diseased muscle. The role of exact fixation and entropy loss in enzyme catalysis will be probed with partial and complete substrates for Coenzyme A transferase and by examining small changes in the size of substituents that are remote from the reacting groups of substrates. Rate and equilibrium constants for formation and breaking of hydrogen bonds in aqueous solution will be examined. The mechanism of calcium internalization and the internal calcium binding site of the calcium ATPase will be characterized. Phosphoryl transfer will be examined by a search for general base catalysis and for catalysis of the cleavage of phosphorylated pyridines by alkaline phosphatase. Acyl cyanides will be examined as substrates for chymotrypsin in an attempt to estimate the role of proton transfer to the leaving group in catalysis; concerted proton transfer to the leaving cyanide is not possible. The mechanism of proton transfer between electronegative atoms will be examined by determining Bronsted plots and isotope effects for general acid and general base catalysis of ester aminolysis involving diffusion-controlled proton transfer. Reactions of acyl halides will be examined to evaluate the importance of acylium ion intermediates and the possibility of a bimolecular substitution mechanism. The mechanism of proton removal from carbon will be studied using the sulfonium ion as activating group to determine if there are changes in transition state structure with changing reactant structure; these compounds are expected to have a small intrinsic barrier for proton transfer that may make such changes more readily detectible.

小组转移反应及其催化的机制将在酶和非酶系统和机制中进行研究将化学能量转化为工作钙质网的钙传输ATPase。这主题在健康和功能中很重要患病的肌肉。精确固定和熵损失的作用酶催化将通过部分和完整探测辅酶A转移酶的底物并检查小远离取代基的大小的变化反应组的底物。速率和平衡常数用于在水溶液中形成和断裂氢键将被检查。钙内在化的机制和钙ATPase的内部钙结合位点将是特征。磷酸化转移将通过搜索检查用于一般基础催化和催化的裂解碱性磷酸酶磷酸化的吡啶。酰基氰化物将被检查为chymotrypsin的底物，以尝试估计质子转移到离开组的作用催化;一致的质子转移到离开氰化物的是不可能。质子转移的机制通过确定Bronsted，将检查电负原子一般酸和一般碱的图和同位素效应酯氨基溶解的催化涉及扩散控制质子转移。将检查酰基卤化物的反应评估酰基离子中间体的重要性和双分子取代机制的可能性。这将研究从碳去除质子的机理硫离子作为激活组，以确定是否存在反应物变化的过渡状态结构的变化结构;这些化合物有望具有较小的内在质子转移的障碍，可能会导致这种更改容易检测到。