Preprints
https://doi.org/10.5194/mr-2021-53
https://doi.org/10.5194/mr-2021-53

  01 Jul 2021

01 Jul 2021

Review status: a revised version of this preprint was accepted for the journal MR and is expected to appear here in due course.

Anomalous Amide Proton Chemical Shifts as Signatures of Hydrogen Bonding to Aromatic Sidechains

Kumaran Baskaran1, Colin W. Wilburn1, Jonathan R. Wedell1, Leonardus M. I. Koharudin2, Eldon L. Ulrich1, Adam D. Schuyler1, Hamid R. Eghbalnia1, Angela M. Gronenborn2, and Jeffrey C. Hoch1 Kumaran Baskaran et al.
  • 1Department of Molecular Biology and Biophysics, UConn Health, 263 Farmington Ave., Farmington, CT 06030-3305 USA
  • 2Department of Structural Biology University of Pittsburgh School of Medicine 3501 Fifth Ave., BST3/Rm. 1050 Pittsburgh, PA 15260 USA

Abstract. Hydrogen bonding between an amide group and the p-π cloud of an aromatic ring was first identified in a protein in the 1980s. Subsequent surveys of high-resolution X-ray crystal structures found multiple instances, but their preponderance was determined to be infrequent. Hydrogen atoms participating in a hydrogen bond to the p-π cloud of an aromatic ring are expected to experience an upfield chemical shift arising from a shielding ring current shift. We survey the Biological Magnetic Resonance Data Bank for amide hydrogens exhibiting unusual shifts as well as corroborating nuclear Overhauser effects between the amide protons and ring protons. We find evidence that Trp residues are more likely to be involved in p-π hydrogen bonds than other aromatic amino acids, whereas His residues are more likely to be involved in hydrogen bonds with a ring nitrogen acting as the hydrogen acceptor. The p-π hydrogen bonds may be more abundant than previously believed. The inclusion in NMR structure refinement protocols of shift effects in amide protons from aromatic side chains, or explicit hydrogen bond restraints between amides and aromatic rings, could improve the local accuracy of side-chain orientations in solution NMR protein structures, but their impact on global accuracy is likely be limited.

Kumaran Baskaran et al.

Status: closed

Comment types: AC – author | RC – referee | CC – community | EC – editor | CEC – chief editor | : Report abuse
  • RC1: 'Comment on mr-2021-53', H.-H. Limbach, 18 Jul 2021
  • RC2: 'Comment on mr-2021-53', Peter Tolstoy, 31 Jul 2021
  • AC1: 'Comment on mr-2021-53', Jeffrey Hoch, 25 Aug 2021

Status: closed

Comment types: AC – author | RC – referee | CC – community | EC – editor | CEC – chief editor | : Report abuse
  • RC1: 'Comment on mr-2021-53', H.-H. Limbach, 18 Jul 2021
  • RC2: 'Comment on mr-2021-53', Peter Tolstoy, 31 Jul 2021
  • AC1: 'Comment on mr-2021-53', Jeffrey Hoch, 25 Aug 2021

Kumaran Baskaran et al.

Kumaran Baskaran et al.

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Short summary
The Biological Magnetic Resonance Data Bank (BMRB) has been used to identify overall trends, for example the relationship between chemical shift and backbone conformation. The BMRB archive has grown so that statistical outliers are sufficiently numerous to afford insights into unusual or unique structural features in proteins. We analyze amide proton chemical shift outliers to gain insights into the occurence of hydrogen bonds between an amide NH and the p-pi cloud of aromatic side-chains.