Enzymes play important roles in many biological processes. Amino acid residues in the active site pocket of an enzyme, which are in direct contact with the substrate(s), are generally believed to be critical for substrate recognition and catalysis. Identifying and understanding how these “catalytic” residues help enzymes achieve enormous rate enhancement has been the focus of many structural and biochemical studies over the past several decades. Recent studies have shown that enzymes are intrinsically dynamic and dynamic coupling between distant structural elements is essential for effective catalysis in modular enzymes. Therefore, distal residues are expected to have impact on enzyme function. However, few studies have investigated the role of distal residues on enzymatic catalysis. In the present study, the effects of distal residue mutations on the catalytic function of an aminoacyl-tRNA synthetase, namely, prolyl-tRNA synthase, were investigated. The present study demonstrates that distal residues significantly contribute to catalysis of the modular Escherichia coli prolyl-tRNA synthetase by maintaining intrinsic protein flexibility.

酶在许多生物过程中发挥着重要作用。与底物直接接触的酶活性位点口袋中的氨基酸残基通常被认为对底物识别和催化至关重要。在过去的几十年里，识别和理解这些“催化”残基如何帮助酶实现巨大的速率提高一直是许多结构和生化研究的重点。最近的研究表明，酶本质上是动态的，远距离结构元素之间的动态耦合对于模块化酶的有效催化至关重要。因此，预计远端残基会对酶功能产生影响。然而，很少有研究调查远端残基对酶催化的作用。在目前的研究中，研究了远端残基突变对氨酰-tRNA 合成酶，即脯氨酰-tRNA 合成酶的催化功能的影响。本研究表明，远端残基显着促进了模块化大肠杆菌脯氨酰-tRNA 合成酶通过保持内在的蛋白质灵活性。