ENZYME MECHANISMS AND ENZYME INHIBITORS

缓蚀剂以氟甲基酮为基础。它的作用机制 抑制丝氨酸蛋白酶(最初是胰凝乳蛋白酶) 将对肽基-氟甲基酮进行研究。问题： 有趣的是：1)所有的肽基-氟甲基酮都形成加合物吗？ 与活性部位丝氨酸？2)如果有，羟基是 产生的半缩醛的电离？3)什么样的相互作用 发生在抑制剂的氨基酸成分和活性成分之间 地点。这些研究将包括动力学研究和x射线。 抑制酶复合体的结晶学。此信息 将用于制定改进设计的策略 其他丝氨酸蛋白酶的抑制剂。最重要的是 人白细胞弹性蛋白酶。一种新的定向活性站点 缓蚀剂将以氟甲基酮为基础合成； 靶点：羧肽酶和血管紧张素转换酶。 利用席夫碱的酶抑制剂也将是 合成，以及酰基转移酶的抑制剂。 蛋氨酸抢救途径。我们将继续调查 5‘-S-甲基腺苷转化为 蛋氨酸。涉及的中间体和酶将是 特色化的。 Lactyl-CoA脱水酶。从C_1中分离出一种酶。 将乳酸辅酶A转化为丙烯酰辅酶A的丙酸。这个 将对这种不寻常反应的机理进行研究，以 确定是否涉及激进的过程，以及角色是什么， 如果有的话，是辅因子(黄素、铁/S中心)。这个 多酶复合体的组成和代谢作用 其中脱水酶是其中的一部分，将被检查。

Inhibitors bases on fluoromethyl ketones. The mechanism of inhibitions of serine proteases (initially chymotrypsin) by peptidyl-fluoreomethyl ketones will be investigated. Questions of interest are: 1) Do all peptidyl-fluoromethyl ketones form adducts with the active site serine? 2) If they do, is the hydroxyl group of the resulting hemiacetal ionized? 3) What kind of interactions occur between amino-acid components of the inhibitor and the active site. These investigations will involve kinetic studies and x-ray crystallography of inhibitor enzyme complexes. This information will be used to develop strategies for the design of improved inhibitors for other serine proteases. Of primary interest is human leucocyte elastase. A new kind of active site directed inhibitor will be synthesized based on fluoromethyl ketones; targets: carboxypeptidase and angiotensin converting enzyme. Inhibitors of enzyme which utilize Schiff bases will also be synthesized, as well as inhibitors for acyl-transfer enzymes. A methionine salvage pathway. We shall continue our investigation of the pathway whereby 5'-S-methyl adenosine is converted to methionine. Intermediates and enzymes involved will be characterized. Lactyl-CoA dehydratase. An enzyme has been isolated from C1. propionicum which converts lactyl-CoA to acrylyl-CoA. The mechanism of this unusual reaction will be investigated, to determine whether a radical process is involved and what the role, if any, is of the cofactors (flavin, Fe/S centers). The composition and metabolic role of the multi-enzyme complex, of which the dehydratase is a part, will be examined.