The low barrier hydrogen bond (LBHB) proposal revisited: The case of the Asp ··· His pair in serine proteases

@article{Schutz2004TheLB,
  title={The low barrier hydrogen bond (LBHB) proposal revisited: The case of the Asp ··· His pair in serine proteases},
  author={Claudia N. Schutz and Arieh Warshel},
  journal={Proteins: Structure},
  year={2004},
  volume={55}
}
The fact that hydrogen bonds (HBs) can provide major stabilization to transition states (TSs) of enzymatic reactions is well known. However, the nature of HB stabilization has been the subject of a significant controversy. It is not entirely clear if this stabilization is associated with electrostatic effects of preorganized dipoles or with delocalized resonance effects of the so‐called low barrier hydrogen bond (LBHB). One of the best test cases for the LBHB proposal is the complex of… 
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128 Citations

Low-barrier hydrogen bond in photoactive yellow protein
TLDR
It is proposed that in the excited state the fast relaxation of the LBHB into a normal hydrogen bond is the trigger for photo-signal propagation to the protein moiety and the mechanism of the formation of LBHBs is proposed.
Direct evidence of a low barrier hydrogen bond in the catalytic triad of a Serine protease
TLDR
NMR evidence is shown that LBHB does exist in NS3, a serine protease from Dengue, and this result will help in understanding the mechanism of the catalytic triad in the important group ofserine proteases.
Low barrier hydrogen bonds in protein structure and function.
Ligand-Induced Proton Transfer and Low-Barrier Hydrogen Bond Revealed by X-ray Crystallography.
TLDR
Three ultrahigh resolution X-ray crystal structures of CTX-M β-lactamase are reported, demonstrating that desolvation of the active site by ligand binding can provide a protein microenvironment conducive to LBHB formation and suggesting that LBHBs may contribute to stabilization of the TS in general acid/base catalysis together with other preorganized features of enzyme active sites.
QM/MM simulation (B3LYP) of the RNase A cleavage-transesterification reaction supports a triester A(N) + D(N) associative mechanism with an O2' H internal proton transfer.
The mechanism of the backbone cleavage-transesterification step of the RNase A enzyme remains controversial even after 60 years of study. We report quantum mechanics/molecule mechanics (QM/MM) free…
Contribution of a Low-Barrier Hydrogen Bond to Catalysis Is Not Significant in Ketosteroid Isomerase
TLDR
The results suggest that the amount of stabilization energy of the reaction intermediate provided by LBHB is small compared with that provided by an ordinary hydrogen bond in KSI, which reduces the binding affinity for the steroid inhibitors.
Spectroscopic and DFT studies of second-sphere variants of the type 1 copper site in azurin: covalent and nonlocal electrostatic contributions to reduction potentials.
TLDR
This study provides a methodology for uncoupling covalency from nonlocal electrostatics, which, when coupled to X-ray crystallographic data, distinguishes specific local interactions from more long-range protein/active interactions, while affording further insight into the second-sphere mechanisms available to the protein to tune the E(0) of electron-transfer sites in biology.
Ab initio QM/MM modelling of acetyl-CoA deprotonation in the enzyme citrate synthase.
A new role of low barrier hydrogen bond in mediating protein stability by small molecules
TLDR
This study has identified a novel approach for designing tubulin degraders, providing a unique example of LBHB function and suggests that designing small molecules to form LBHBs with protein residues resulting in the highly specific degradation of a target protein could be a new strategy for drug development.
Low-barrier hydrogen bonds in proteins
Hydrogen bonding interactions are one of the most important chemical interactions among materials, especially biological materials, which help confer specificity, which is crucial for their efficient…
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References

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