Revealing arginine-cysteine and glycine-cysteine NOS linkages by a systematic re-evaluation of protein structures.

ABSTRACT: Nitrogen-oxygen-sulfur (NOS) linkages act as allosteric redox switches, modulating enzymatic activity in response to redox fluctuations. While NOS linkages in proteins were once assumed to occur only between lysine and cysteine, our investigation shows that these bonds extend beyond the well-studied lysine-NOS-cysteine examples. By systematically analyzing over 86,000 high-resolution X-ray protein structures, we uncovered 69 additional NOS bonds, including arginine-NOS-cysteine and glycine-NOS-cysteine. Our pipeline integrates machine learning, quantum-mechanical calculations, and high-resolution X-ray crystallographic data to systematically detect these subtle covalent interactions and identify key predictive descriptors for their formation. The discovery of these previously unrecognized

SUBMITTER: Bazzi S 

PROVIDER: S-EPMC12075730 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature