Abstract

Since the 1960s, chemists have known about an unusual type of hydrogen bond: one that can form between the amide hydrogen and the carbonyl oxygen in the same amino acid. But it’s been hard to show that this interaction, called the C5 hydrogen bond, matters in proteins, not just individual amino acids. Now, biochemistry professor Ronald T. Raines and graduate student Robert W. Newberry of the University of Wisconsin, Madison, report experimental and computational evidence that this hydrogen bond indeed helps stabilize proteins—significantly in some cases (Nat. Chem. Biol. 2016, DOI: 10.1038/nchembio.2206). “It has been problematic to quantify the energetic consequence of this H-bond, particularly in systems larger than a dipeptide where numerous other factors come into play,” says Steve Scheiner of Utah State University who studies hydrogen bonding. The new work “takes a major step toward unambiguously verifying the presence of this H-bond, as well as offering some quantitative

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