Open AccessPEGylation Increases the Strength of a Nearby NH-π Hydrogen Bond in the WW Domain
Author(s) -
Steven R. E. Draper,
Zachary Jones,
Seth O Earl,
Nicholas A. Dalley,
Dallin S Ashton,
Anthony J Carter,
Benjamin M Conover,
Joshua L. Price
Publication year - 2021
Publication title -
biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.43
H-Index - 253
eISSN - 1520-4995
pISSN - 0006-2960
DOI - 10.1021/acs.biochem.1c00132
Subject(s) - chemistry , steric effects , pegylation , hydrogen bond , amide , ww domain , polarizability , side chain , stereochemistry , crystallography , molecule , organic chemistry , biochemistry , polyethylene glycol , gene , polymer
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.