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Updated: Mar 15, 2026

Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins
Published on: October 4, 2017
Preferred Hydrogen-Bonding Partners of Cysteine: Implications for Regulating Cys Functions
Karine Mazmanian1,2,3, Karen Sargsyan1, Cédric Grauffel1
1Institute of Biomedical Sciences, Academia Sinica , Taipei 11529, Taiwan.
Abstract:
The hydrogen-bonding interactions of cysteine, which can serve as a hydrogen-bond donor and/or acceptor, play a central role in cysteine's diverse functional roles in proteins. They affect the balance between the neutral thiol (SH) or thiolate (S-) and the charge distribution in the rate-limiting transition state of a reaction. Despite their importance, no study has determined the preferred hydrogen-bonding partners of cysteine serving as a hydrogen-bond donor or acceptor. By computing the free energy for displacing a peptide backbone hydrogen-bonded to cysteine with amino acid side chains in various protein environments, we have evaluated how the strength of the hydrogen bond to the cysteine thiol/thiolate depends on its hydrogen-bonding partner and its local environment. The predicted hydrogen-bonding partners preferred by cysteine are consistent with the hydrogen-bonding interactions made by cysteines in 9138 nonredundant X-ray structures. Our results suggest a mechanism to regulate the reactivity of cysteines and a strategy to design drugs based on the hydrogen-bonding preference of cysteine.
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