The catalytic residues of an enzyme comprise the amino acids located in the active center responsible for accelerating the enzyme-catalyzed reaction. These residues lower the activation energy of reactions by performing several catalytic functions. Decades of enzymology research has established general themes regarding the roles of specific residues in these catalytic reactions, but it has been more difficult to explore these roles in a more systematic way. Here, we review the data on the catalytic residues of 648 enzymes, as annotated in the Mechanism and Catalytic Site Atlas (M-CSA), and compare our results with those in previous studies. We structured this analysis around three key properties of the catalytic residues: amino acid type, catalytic function, and sequence conservation in homologous proteins. As expected, we observed that catalysis is mostly accomplished by a small set of residues performing a limited number of catalytic functions. Catalytic residues are typically highly conserved, but to a smaller degree in homologues that perform different reactions or are nonenzymes (pseudoenzymes). Cross-analysis yielded further insights revealing which residues perform particular functions and how often. We obtained more detailed specificity rules for certain functions by identifying the chemical group upon which the residue acts. Finally, we show the mutation tolerance of the catalytic residues based on their roles. The characterization of the catalytic residues, their functions, and conservation, as presented here, is key to understanding the impact of mutations in evolution, disease, and enzyme design. The tools developed for this analysis are available at the M-CSA website and allow for user specific analysis of the same data.

中文翻译：

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酶催化残基的功能和保守性的全局分析。

酶的催化残基包含位于活性中心的氨基酸，负责加速酶催化的反应。这些残基通过执行多种催化功能而降低了反应的活化能。数十年来的酶学研究已经建立了关于特定残基在这些催化反应中的作用的一般主题，但是以更系统的方式探索这些作用变得更加困难。在这里，我们回顾了《机理和催化位点图集》（M-CSA）中注释的648种酶的催化残基数据，并将我们的结果与以前的研究进行了比较。我们围绕催化残基的三个关键特性构建了此分析：氨基酸类型，催化功能和同源蛋白中的序列保守性。不出所料 我们观察到，催化作用主要是由一小组执行有限数量催化作用的残基完成的。催化残基通常是高度保守的，但在执行不同反应或为非酶（假酶）的同系物中，其程度较小。交叉分析产生了进一步的见解，揭示了哪些残基执行特定功能以及执行频率。通过确定残基所作用的化学基团，我们获得了针对某些功能的更详细的特异性规则。最后，我们根据催化残基的作用显示了其突变耐受性。如此处所述，催化残基的表征，其功能和保守性是理解突变对进化，疾病和酶设计的影响的关键。