Intrinsic folding of the cysteine residue: competition between folded and extended forms mediated by the –SH group
Résumé
A dual microwave and optical spectroscopic study of a capped cysteine amino acid isolated in a supersonic expansion, combined with quantum chemistry modelling, enabled us to characterize the conformational preferences of Cys embedded in a protein chain. IR/UV double resonance spectroscopy provided evidence for the coexistence of two conformers, assigned to folded and extended backbones (with classical C7 and C5 backbone H-bonding respectively), each of them additionally stabilized by specific main-chain/side-chain H-bonding, where the sulfur atom essentially plays the role of H-bond acceptor. The folded structure was confirmed by microwave spectroscopy, which demonstrated the validity of the DFT-D methods currently used in the field. These structural and spectroscopic results, complemented by a theoretical Natural Bond Orbital analysis, enabled us to document the capacity of the weakly polar –CH$_2$–SH side chain of Cys to adapt itself to the intrinsic local preferences of the peptide backbone, i.e., a $\gamma$-turn or a $\beta$-sheet extended secondary structure. The corresponding local H-bonding bridges the side chain acceptor S atom to the backbone NH donor site of the same or the next residue along the chain, through a 5- or a 6-membered ring respectively
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