ENZYME MECHANISMS AND ENZYME INHIBITORS

缓蚀剂以氟甲基酮为基础。 的机理 抑制丝氨酸蛋白酶（最初是胰凝乳蛋白酶）， 将研究肽基-氟甲基酮。 问题 感兴趣是：1）所有的肽基-氟甲基酮都形成加合物吗 有丝氨酸活性位点吗 2)如果是的话， 产生的半缩醛离子化了吗 3)什么样的互动 发生在抑制剂和活性物质的氨基酸组分之间 绝佳的价钱 这些研究将涉及动力学研究和X射线 抑制剂酶复合物的晶体学。 这些信息 将被用来制定战略， 其他丝氨酸蛋白酶的抑制剂。 最感兴趣的是 人白细胞弹性蛋白酶。 一种新的活性中心定向 以氟甲基酮为原料合成缓蚀剂; 靶点：羧肽酶和血管紧张素转换酶。 利用席夫碱的酶的抑制剂也将是 合成的，以及酰基转移酶的抑制剂。 蛋氨酸补救途径。 我们会继续调查 5 '-S-甲基腺苷转化为 蛋氨酸。 所涉及的中间体和酶将是 表征了 乳酰辅酶A脱氢酶。 已从C1中分离出一种酶。 propionicum将乳酰CoA转化为丙烯酰CoA。 的 这种不寻常的反应机制将被调查， 确定是否涉及激进的过程及其作用， 如果有的话，是辅因子（黄素，Fe/S中心）。 的 多酶复合物的组成和代谢作用， 其中所述酶是一部分，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.