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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structure of a serine protease poised to resynthesize a peptide bond
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Structure of a serine protease poised to resynthesize a peptide bond

机译：丝氨酸蛋白酶的结构准备重新合成肽键

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摘要

The serine proteases are among the most thoroughly studied enzymes, and numerous crystal structures representing the enzyme-substrate complex and intermediates in the hydrolysis reactions have been reported. Some aspects of the catalytic mechanism remain controversial, however, especially the role of conformational changes in the reaction. We describe here a high-resolution (1.46 A) crystal structure of a complex formed between a cleaved form of bovine pancreatic trypsin inhibitor (BPTI) and a catalytically inactive trypsin variant with the BPTI cleavage site ideally positioned in the active site for resynthesis of the peptide bond. This structure defines the positions of the newly generated amino and carboxyl groups following the 2 steps in the hydroiytic reaction. Comparison of this structure with those representing other intermediates in the reaction demonstrates that the residues of the catalytic triad are positioned to promote each step of both the forward and reverse reaction with remarkably little motion and with conservation of hydrogen-bonding interactions. The results also provide insights into the mechanism by which inhibitors like BPTi normally resist hydrolysis when bound to their target proteases.
机译：丝氨酸蛋白酶是最深入研究的酶之一，并且已经报道了代表酶-底物复合物和水解反应中间体的许多晶体结构。然而，催化机理的某些方面仍存在争议，特别是构象变化在反应中的作用。我们在此描述高分辨率（1.46 A）晶体结构的牛胰胰蛋白酶抑制剂（BPTI）的裂解形式和催化失活的胰蛋白酶变体之间形成的复合物，BPTI裂解位点理想地位于活性位点以重新合成肽键。该结构定义了在水解反应中的两个步骤之后新产生的氨基和羧基的位置。将该结构与代表反应中其他中间体的那些结构进行比较表明，催化三单元组的残基被定位为以显着很少的运动并且保留氢键相互作用来促进正向和反向反应的每个步骤。该结果还提供了与BPTi等抑制剂结合至其靶蛋白酶时通常能抵抗水解的机理的见解。

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