On the Case of the Misplaced Hydrogens
Dr. Prashasti Kumar
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029 USA
Search for more papers by this authorProf. Pratul K. Agarwal
Arium BioLabs LLC, Knoxville, TN, 37932 USA
Department of Physiological Sciences and High-Performance Computing Center, Oklahoma State University, Stillwater, OK 74078 USA
Search for more papers by this authorCorresponding Author
Dr. Matthew J. Cuneo
Department of Structural Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN, 38103 USA
Search for more papers by this authorDr. Prashasti Kumar
Department of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029 USA
Search for more papers by this authorProf. Pratul K. Agarwal
Arium BioLabs LLC, Knoxville, TN, 37932 USA
Department of Physiological Sciences and High-Performance Computing Center, Oklahoma State University, Stillwater, OK 74078 USA
Search for more papers by this authorCorresponding Author
Dr. Matthew J. Cuneo
Department of Structural Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Pl, Memphis, TN, 38103 USA
Search for more papers by this authorGraphical Abstract
The position of a hydrogen in a short hydrogen bond (SHB) is indicative of the bond strength. Yet, few techniques can locate a hydrogen atom in either canonical, or unusually strong, low-barrier hydrogen bonds. This has led to discrepancies among simulations and biochemical studies. We review two examples of SHB-containing proteins to gain insights into the energetic role of these bonds.
Abstract
Few other elements play a more central role in biology than hydrogen. The interactions, bonding and movement of hydrogen atoms are central to biological catalysis, structure and function. Yet owing to the elusive nature of a single hydrogen atom few experimental and computational techniques can precisely determine its location. This is exemplified in short hydrogen bonds (SHBs) where the location of the hydrogen atom is indicative of the underlying strength of the bonds, which can vary from 1–5 kcal/mol in canonical hydrogen bonds, to an almost covalent nature in single-well hydrogen bonds. Owing to the often-times inferred position of hydrogen, the role of SHBs in biology has remained highly contested and debated. This has also led to discrepancies in computational, biochemical and structural studies of proteins thought to use SHBs in performing chemistry and stabilizing interactions. Herein, we discuss in detail two distinct examples, namely the conserved catalytic triad and the photoreceptor, photoactive yellow protein, where studies of these SHB-containing systems have permitted contextualization of the role these unique hydrogen bonds play in biology.
Conflict of interest
The authors declare no conflict of interest.
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