Cysteine proteases and how YabG fits into clan CD of the MEROPS database

ABSTRACT Cysteine proteases are hydrolases that share a common catalytic mechanism involving a nucleophilic cysteine thiol in a catalytic dyad or triad. Here, we review the current clans that make up the cysteine proteases in the MEROPS database as of March 2025. We also discuss cysteine proteases made by C. difficile, with a particular focus on recent analysis of the sporulation-specific protease, YabG, that supports its reclassification into clan CD of the MEROPS protease database. YabG is a highly conserved sporulation-specific protease that, until more recently, has been mostly studied in B. subtilis, where YabG is important for processing coat proteins. In C. difficile, YabG processes proteins required for spore germination and is important in coat/exosporium protein expression.