4.4 Review

On the Case of the Misplaced Hydrogens

Journal

CHEMBIOCHEM
Volume 22, Issue 2, Pages 288-297

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.202000376

Keywords

catalytic triads; hydrogen bonds; low-barrier hydrogen bonds; photoactive yellow proteins; short ionic hydrogen bonds

Funding

  1. National Institute of General Medical Sciences of the National Institutes of Health [GM105978]
  2. American Lebanese Syrian Associated Charities (ALSAC)
  3. St. Jude Children's Research Hospital

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Hydrogen plays a central role in biology, but due to difficulties in precisely determining its location, research on short hydrogen bonds has been controversial. Studies suggest that unique hydrogen bonds play a special role in biology.
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.

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