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

ABSTRACT: 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.

SUBMITTER: Draper SRE

PROVIDER: S-EPMC8406554 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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

Draper Steven R E SRE Jones Zachary B ZB Earl Seth O SO Dalley Nicholas A NA Ashton Dallin S DS Carter Anthony J AJ Conover Benjamin M BM Price Joshua L JL

Biochemistry 20210617 26

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-chai ...[more]

PMID: 34137579

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