从胰蛋白酶反应中间体的原子分辨率结构洞察丝氨酸蛋白酶机制。
Insights into the serine protease mechanism from atomic resolution structures of trypsin reaction intermediates.
作者信息
Radisky Evette S, Lee Justin M, Lu Chia-Jung Karen, Koshland Daniel E
机构信息
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
出版信息
Proc Natl Acad Sci U S A. 2006 May 2;103(18):6835-40. doi: 10.1073/pnas.0601910103. Epub 2006 Apr 24.
Abstract
Atomic resolution structures of trypsin acyl-enzymes and a tetrahedral intermediate analog, along with previously solved structures representing the Michaelis complex, are used to reconstruct events in the catalytic cycle of this classic serine protease. Structural comparisons provide insight into active site adjustments involved in catalysis. Subtle motions of the catalytic serine and histidine residues coordinated with translation of the substrate reaction center are seen to favor the forward progress of the acylation reaction. The structures also clarify the attack trajectory of the hydrolytic water in the deacylation reaction.
摘要
胰蛋白酶酰基酶和四面体中间体类似物的原子分辨率结构，以及先前解析的代表米氏复合物的结构，被用于重建这种经典丝氨酸蛋白酶催化循环中的事件。结构比较有助于深入了解催化过程中涉及的活性位点调整。观察到催化丝氨酸和组氨酸残基的细微运动与底物反应中心的平移相协调，有利于酰化反应的正向进行。这些结构还阐明了脱酰化反应中水解水的攻击轨迹。
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