Quantitative Analysis of Multiplex H-Bonds

Esther S. Brielle, Isaiah T. Arkin

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

H-bonding is the predominant geometrical determinant of biomolecular structure and interactions. As such, considerable analyses have been undertaken to study its detailed energetics. The focus, however, has been mostly reserved for H-bonds comprising a single donor and a single acceptor. Herein, we measure the prevalence and energetics of multiplex H-bonds that are formed between three or more groups. We show that 92% of all transmembrane helices have at least one non-canonical H-bond formed by a serine or threonine residue whose hydroxyl side chain H-bonds to an over-coordinated carbonyl oxygen at position i-4, i-3, or i in the sequence. Isotope-edited FTIR spectroscopy, coupled with DFT calculations, enables us to determine the bond enthalpies, pointing to values that are up to 127% higher than that of a single canonical H-bond. We propose that these strong H-bonds serve to stabilize serine and threonine residues in hydrophobic environments while concomitantly providing them flexibility between different configurations, which may be necessary for function.

Original languageAmerican English
Pages (from-to)14150-14157
Number of pages8
JournalJournal of the American Chemical Society
Volume142
Issue number33
DOIs
StatePublished - 19 Aug 2020

Bibliographical note

Funding Information:
The authors thank Prof. A. Senes for invaluable discussions. The authors thank Sophie De-Botton for help synthesizing the isotopically labeled valine. This work was supported in part by grants from the United States-Israel Binational Science Foundation, the Israeli Science Foundation, and the Israeli Ministry of Science and Technology.

Publisher Copyright:
Copyright © 2020 American Chemical Society.

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