Analysis of crystal structures of aspartic proteinases: On the role of amino acid residues adjacent to the catalytic site of pepsin-like enzymes
Analysis of crystal structures of aspartic proteinases: On the role of amino acid residues adjacent to the catalytic site of pepsin-like enzymes
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DOI：
10.1110/ps.ps.25801
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发表时间：
2001-12-01
期刊：
影响因子：
8
通讯作者：
Rumsh, LD
中科院分区：
文献类型：
--
作者：
Andreeva, NS;Rumsh, LD
为了阐明胃蛋白酶样酶的催化位点附近的氨基酸残基的作用，我们分析和比较了这些酶的晶体结构，它们与抑制剂的复合物，以及活性位点区域的酶原（共82个结构）。除了位于活性羧基之间并在催化反应中起亲核作用的水分子（WI）外，发现活性基团附近的另一个水分子（W2）是完全保守的。该水分子在活性位点瓣和配体结合上的活性羧基之间的氢键残基链的形成中起重要作用。这些数据提出了一种新的方法来理解催化位点周围的残基的作用，这可以帮助催化反应的发展。邻近活性羧基的基团的影响表现为在pH 1.0下的胃蛋白酶活性。胃蛋白酶样酶及其突变体的一些功能进行了讨论的框架内的方法。
To elucidate the role of amino acid residues adjacent to the catalytic site of pepsin-like enzymes, we analyzed and compared the crystal structures of these enzymes, their complexes with inhibitors, and zymogens in the active site area (a total of 82 structures). In addition to the water molecule (WI) located between the active carboxyls and playing a role of the nucleophile during catalytic reaction, another water molecule (W2) at the vicinity of the active groups was found to be completely conserved. This water molecule plays an essential role in formation of a chain of hydrogen-bonded residues between the active site flap and the active carboxyls on ligand binding. These data suggest a new approach to understanding the role of residues around the catalytic site, which can assist the development of the catalytic reaction. The influence of groups adjacent to the active carboxyls is manifested by pepsin activity at pH 1.0. Some features of pepsin-like enzymes and their mutants are discussed in the framework of the approach.