Istituto di Cristallografia - Consiglio Nazionale delle Ricerche, Trieste, Italy.
J Enzyme Inhib Med Chem. 2023 Dec;38(1):2245168. doi: 10.1080/14756366.2023.2245168.
The formal mechanism of linear mixed and non-competitive enzyme inhibition implies the binding of inhibitors to both the active site of the free enzyme in competition with the substrate, and to an allosteric site on the enzyme-substrate complex. However, it is evident from a review of the scientific literature that the two-site mechanism is frequently mistaken as the actual underlying mechanism of mixed inhibition. In this study, we conducted a comprehensive assessment of the mechanistic relevance of this type of inhibition using a statistical approach. By combining a statistical analysis of the inhibition cases documented in the BRENDA database with a theoretical investigation of inhibition models, we conclude that mixed inhibitors exclusively bind to the active site of enzymes. Hence ruling out any implication of allosteric sites and depriving the two-site model of any mechanistic relevance.
线性混合和非竞争性酶抑制的正式机制意味着抑制剂与游离酶的活性部位结合，与酶-底物复合物上的变构部位结合，与底物竞争。然而，从对科学文献的回顾中可以明显看出，双位点机制经常被误认为是混合抑制的实际潜在机制。在这项研究中，我们使用统计方法对这种抑制类型的机制相关性进行了全面评估。通过将 BRENDA 数据库中记录的抑制案例的统计分析与抑制模型的理论研究相结合，我们得出结论，混合抑制剂仅与酶的活性部位结合。因此，排除了变构部位的任何影响，并使双位点模型失去了任何机制相关性。
