Department of Molecular Medicine, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd, MDC 3522, Tampa, Florida 33612, United States.
Department of Molecular Medicine, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd, MDC 3522, Tampa, Florida 33612, United States.
Biochim Biophys Acta Proteins Proteom. 2021 Jan;1869(1):140557. doi: 10.1016/j.bbapap.2020.140557. Epub 2020 Oct 23.
Low-barrier hydrogen bonds (LBHBs) are a special type of short hydrogen bond (HB) that is characterized by the equal sharing of a hydrogen atom. The existence and catalytic role of LBHBs in proteins has been intensely contested. Advancements in X-ray and neutron diffraction methods has revealed delocalized hydrogen atoms involved in potential LBHBs in a number of proteins, while also demonstrating that short HBs are not necessarily LBHBs. More importantly, a series of experiments on ketosteroid isomerase (KSI) have suggested that LBHBs are significantly stronger than standard HBs in the protein microenvironment in terms of enthalpy, but not free energy. The discrepancy between the enthalpy and free energy of LBHBs offers clues to the challenges, and potential solutions, of the LBHB debate, where the unique strength of LBHBs plays a special role in the kinetic processes of enzyme function and structure, together with other molecular forces in a pre-organized environment.
低能垒氢键 (LBHBs) 是一种特殊类型的短氢键 (HB)，其特征在于氢原子的平均共享。LBHBs 在蛋白质中的存在和催化作用一直存在争议。X 射线和中子衍射方法的进步揭示了许多蛋白质中涉及潜在 LBHBs 的离域氢原子，同时也表明短 HB 不一定是 LBHBs。更重要的是，一系列关于酮固醇异构酶 (KSI) 的实验表明，在蛋白质微环境中，LBHBs 在焓方面比标准 HB 强得多，但在自由能方面则不然。LBHBs 的焓和自由能之间的差异为 LBHB 争论提供了线索，LBHBs 的独特强度在酶功能和结构的动力学过程中以及在预组织环境中的其他分子力中发挥着特殊作用。
