Wu Chia-Hua, Ito Keigo, Buytendyk Allyson M, Bowen K H, Wu Judy I
Department of Chemistry, University of Houston , Houston, Texas 77204, United States.
Department of Chemistry, Johns Hopkins University , Baltimore, Maryland 21218, United States.
Biochemistry. 2017 Aug 22;56(33):4318-4322. doi: 10.1021/acs.biochem.7b00395. Epub 2017 Aug 1.
Surprisingly large resonance-assistance effects may explain how some enzymes form extremely short, strong hydrogen bonds to stabilize reactive oxyanion intermediates and facilitate catalysis. Computational models for several enzymic residue-substrate interactions reveal that when a π-conjugated, hydrogen bond donor (XH) forms a hydrogen bond to a charged substrate (Y), XH can become significantly more π-electron delocalized, and this "extra" stabilization may boost the [XH···Y] hydrogen bond strength by ≥15 kcal/mol. This reciprocal relationship departs from the widespread pK concept (i.e., the idea that short, strong hydrogen bonds form when the interacting moieties have matching pK values), which has been the rationale for enzymic acid-base reactions. The findings presented here provide new insight into how short, strong hydrogen bonds could form in enzymes.
令人惊讶的是，较大的共振辅助效应或许可以解释某些酶如何形成极短且强的氢键，以稳定反应性氧阴离子中间体并促进催化作用。几种酶残基 - 底物相互作用的计算模型表明，当一个π共轭的氢键供体（XH）与带电荷的底物（Y）形成氢键时，XH的π电子离域程度会显著增加，这种“额外”的稳定性可能会使[XH···Y]氢键强度提高≥15千卡/摩尔。这种相互关系不同于广泛应用的pK概念（即相互作用基团具有匹配的pK值时形成短而强的氢键的观点），而pK概念一直是酶酸碱反应的理论基础。此处呈现的研究结果为酶中如何形成短而强的氢键提供了新的见解。
