Strength of NH···S Hydrogen Bonds in Methionine Residues Revealed by Gas-Phase IR/UV Spectroscopy.

Despite of being ubiquitous in proteins, NHbackbone···S hydrogen bonds linking the sulfur atom of methionine or cysteine to backbone NH groups remain poorly documented. Here, we report vibrationally resolved IR NH stretch spectra of two methionine-containing dipeptides (Ac-Phe-Met-NH2 and Ac-Met-Phe-NH2). The conformations observed for both molecules, assigned with the help of DFT-D quantum chemistry, provide spectroscopic evidence for the formation of NHbackbone···S H-bonds, surprisingly strong enough to challenge the classical intrabackbone NH···O═C H-bonds. The methionine side chain is found to fold locally, forming a H-bond with the neighboring amide groups (NH(i) or NH(i+1)). Comparison with protein data bank structural information shows that such a local folding is also common in proteins where it concerns 24% of the methionine residues that have a sulfur atom linked to a backbone NH group. This convergence between the strength of these NH···S H-bonds and protein structural data illustrates their contribution to the stability of protein chains.