Authors: Goldsztejn, Gildas; Mundlapati, Venkateswara Rao; Brenner, Valerie; Gloaguen, Eric; Mons, Michel; Cabezas, Carlos; Leon, Iker; Luis Alonso, Jose

Contribution: Article


Publication date: 2020/09/28

DOI: 10.1039/d0cp03136d

Abstract: 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 -CH2-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.