第二章酶学基础综述.pptVIP

邻近效应 10-3较10-4反应速度增加107 定向效应 速度增加1011 4.“应力”和“形变” 活性部位严格按序排列着的带电基团的作用，引起底物共价键中电子重新分布并带来“应力”，甚至“形变” 。 水解速度增加108倍 5.酶对反应过渡状态的结合作用： 反应速率与形成过渡状态稳定性密切相关，容易形成过渡态的反应，速率都比较快。 在酶催化的反应巾，酶与反应过渡状态的亲和能力远大于酶与底物或产物的亲和能力。酶对底物过渡状态的这种稳定作用，有利于反应进行。 6．多功能催化与协同作用： 酶的活性中心部位，一般都有多个起催化基团，在空间有特殊的排列和取向，可以对底物起到协同作用，从而使底物达到最佳反应状态。 胰凝乳蛋白酶活性中心的电荷中继网Asp102-His57-Ser195 7．活性部位疏水环境的作用 疏水区介电常数低，底物分子与催化基团之间作用的力更强，有助于酶促反应。 由于特殊的微环境，在一个溶液中可以同时存在高浓度的酸和碱，以在反应中起酸或碱的作用。 The peptide bond to be cleaved is positioned by the binding of the side chain of an adjacent hydrophobic residue in a special hydrophobic pocket. Asp102 functions only to orient His57. Formation of the ES complex E S ES1 Formation of ES1 His57 acts as a general base in deprotonating Ser195, the alkoxide ion then acts as a nucleophile, attacking the carbonyl carbon. Ser195 forms a covalent bond with the peptide (acylation) to be cleaved. a trigonal C is turned into a tetrahedral C. The tetrahedral oxyanion intermediate is stabilized by the NHs of Gly193 and Ser195 Preferential binding of the transition state: oxyanion hole stabilization of the negatively charged tetrahedral intermediate of the transition state. Pre-acylation ES1 oxyanion hole The amine product is then released from the active site with the formation of an acyl-enzyme covalent intermediate. His57 acts as a general acid in cleaving the peptide bond. Acylation Releasing of P1 ES1 Acyl-E Water (the second substrate) then enters the active site. Entering of S2 Acyl-E E’S2 His57 acts as a general base again, allowing water to attack the acyl-enzyme intermediate, forming another tetrahedral oxyanion intermediate, again stabilized by the NHs of Gly193 and Ser195 (similar to step 2) Pre-deacylation E’S2 His57 acts as a general acid again in breaking the covalent bond between the enzyme and substrate (deacylation) (similar to Step 3). Deacylation EP2 The second product (an acid) is released from the active site, with the enzyme recovered to its original stat