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PEGylation Increases the Strength of a Nearby NH-π Hydrogen Bond in the WW Domain.

Steven R E DraperZachary B JonesSeth O EarlNicholas A DalleyDallin S AshtonAnthony J CarterBenjamin M ConoverJoshua L Price
Published in: Biochemistry (2021)
Here we show that an NH-π interaction between a highly conserved Asn and a nearby Trp stabilizes the WW domain of the human protein Pin1. The strength of this NH-π interaction depends on the structure of the arene, with NH-π interactions involving Trp or naphthylalanine being substantially more stabilizing than those involving Tyr or Phe. Calculations suggest arene size and polarizability are key structural determinants of NH-π interaction strength. Methylation or PEGylation of the Asn side-chain amide nitrogen each strengthens the associated NH-π interaction, though likely for different reasons. We hypothesize that methylation introduces steric clashes that destabilize conformations in which the NH-π interaction is not possible, whereas PEGylation strengthens the NH-π interaction via localized desolvation of the protein surface.
Keyphrases
  • room temperature
  • perovskite solar cells
  • endothelial cells
  • genome wide
  • dna methylation
  • small molecule
  • protein protein
  • binding protein
  • water soluble