How the Same Core Catalytic Machinery Catalyzes 17 Different Reactions: the Serine-Histidine-Aspartate Catalytic Triad of α/β-Hydrolase Fold Enzymes.
How the Same Core Catalytic Machinery Catalyzes 17 Different Reactions: the Serine-Histidine-Aspartate Catalytic Triad of α/β-Hydrolase Fold Enzymes.
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DOI：
10.1021/acscatal.5b01539
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发表时间：
2015-10-02
期刊：
影响因子：
12.9
通讯作者：
Kazlauskas RJ
中科院分区：
文献类型：
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作者：
Rauwerdink A;Kazlauskas RJ
同一家族中的酶通常催化不同的反应。在某些情况下，这种多样性源于不同的催化机制，但在其他情况下，机制是相同的;然而，酶催化不同的反应。在这篇综述中，我们研究了包含丝氨酸-组氨酸-天冬氨酸催化三联体的α/β-水解酶折叠酶的子集。尽管具有相同的蛋白质折叠和相同的核心催化机制，这些酶催化17种不同的反应机制。最常见的反应是C-O、C-N和C-C键的水解（酶分类（EC）第3组），但其他酶是氧化还原酶（EC第1组）、酰基转移酶（EC第2组）、裂解酶（EC第4组）或异构酶（EC第5组）。水解反应通常遵循经典的酯酶机制，但在酰基酶中间体的形成或裂解不同的情况下，会发生八种变化。其余八种机制是裂解酶型消除反应，其不具有酰基酶中间体，并且在四种情况下，甚至不需要催化丝氨酸。来自相同催化三联体的这种机制多样性源于酶结合不同底物的能力，源于这些新底物对不同化学步骤的要求，并且仅在约一半的情况下，源于活性位点中的额外氢键伴侣或额外的一般酸/碱。这种详细的分析表明，结合差异和非催化残基创造了新的机制，对于理解和设计有效的酶至关重要。
Enzymes within a family often catalyze different reactions. In some cases, this variety stems from different catalytic machinery, but in other cases the machinery is identical; nevertheless, the enzymes catalyze different reactions. In this review, we examine the subset of α/β-hydrolase fold enzymes that contain the serine-histidine-aspartate catalytic triad. In spite of having the same protein fold and the same core catalytic machinery, these enzymes catalyze seventeen different reaction mechanisms. The most common reactions are hydrolysis of C–O, C–N and C–C bonds (Enzyme Classification (EC) group 3), but other enzymes are oxidoreductases (EC group 1), acyl transferases (EC group 2), lyases (EC group 4) or isomerases (EC group 5). Hydrolysis reactions often follow the canonical esterase mechanism, but eight variations occur where either the formation or cleavage of the acyl enzyme intermediate differs. The remaining eight mechanisms are lyase-type elimination reactions, which do not have an acyl enzyme intermediate and, in four cases, do not even require the catalytic serine. This diversity of mechanisms from the same catalytic triad stems from the ability of the enzymes to bind different substrates, from the requirements for different chemical steps imposed by these new substrates and, only in about half of the cases, from additional hydrogen bond partners or additional general acids/bases in the active site. This detailed analysis shows that binding differences and non-catalytic residues create new mechanisms and are essential for understanding and designing efficient enzymes.