Protein structural change upon ligand binding correlates with enzymatic reaction mechanism
Protein structural change upon ligand binding correlates with enzymatic reaction mechanism
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DOI：
10.1016/j.jmb.2008.04.019
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发表时间：
2008-06-06
影响因子：
5.6
通讯作者：
Kidera, Akinori
中科院分区：
文献类型：
--
作者：
Koike, Ryotaro;Amemiya, Takayuki;Kidera, Akinori
通过对62种非冗余酶的数据库分析，研究了酶响应配体结合的总体结构变化，这些酶的配体未结合和配体结合形式可在蛋白质数据库中获得。分析的结果表明，转移酶往往进行大的刚体域运动后，配体结合，而其他酶，最典型的水解酶，改变它们的结构在很小的程度上。还发现底物分子的溶剂可及性在转移酶中低，但在水解酶中高。这些差异是由酶促反应机制解释的。转移酶反应需要催化基团与水环境绝缘，因此转移酶通过关闭裂缝将配体分子埋在蛋白质内。另一方面，水解酶反应涉及周围的水分子，发生在蛋白质表面，只需要很小的结构变化。(c)2008爱思唯尔有限公司保留所有权利。
Overall structural changes of enzymes in response to ligand binding were investigated by database analysis of 62 non-redundant enzymes whose ligand-unbound and ligand-bound forms were available in the Protein Data Bank. The results of analysis indicate that transferases often undergo large rigid-body domain motions upon ligand binding, while other enzymes, most typically, hydrolases, change their structures to a small extent. It was also found that the solvent accessibility of the substrate molecule was low in transferases but high in hydrolases. These differences are explained by the enzymatic reaction mechanisms. The transferase reaction requires the catalytic groups to be insulated from the water environment, and thus transferases bury the ligand molecule inside the protein by closing the cleft. On the other hand, the hydrolase reaction involves the surrounding water molecules and occurs at the protein surface, requiring only a small structural change. (c) 2008 Elsevier Ltd. All rights reserved.