CONFORMATIONAL SUBSTATES DETERM OF SUBSTRATE SPECIFICITY OF ALPHA LYTIC PROTEASE

？-溶酶是一种丝氨酸蛋白酶，是多肽所特有的。 含有一个小疏水侧链的位置正好 N端连接到水解键(P1位置)。结构性 利用跃迁分析反应机理是可能的 状态类似物，形成共价加合物的多肽抑制剂 在P1残基和活性部位丝氨酸之间。结晶学 我们实验室的研究表明，底物中的氨基酸结合 当与抑制剂结合时，口袋采用不同的构象 不同的P1侧链。即Met到Ala突变(M190A)允许 P1侧链的高效底物结合 苯丙氨酸或小至丙氨酸，有结合袋肿胀 或者缩水以适应变化。我们希望对这些进行研究 构象变化。

?-Lytic protease, a serine protease, is specific for peptides containing a small hydrophobic side chain at the position just N-terminal to the hydrolyzed bond (the P1 position). Structural analysis of the reaction mechanism is possible by using transition state analogues, peptide inhibitors that form a covalent adduct between the P1 residue and the active site serine. Crystallographic studies in our lab show that amino acids in the substrate binding pocket adopt different conformations when bound to inhibitors with different P1 sidechains. i.e., a Met to Ala mutation (M190A) allows productive substrate binding for P1 sidechains as large as phenylalanine or as small as alanine, with the binding pocket swelling or shrinking to accommodate the change. We wish to study these conformational changes.