biostudies-literatureGuevara TMinisterstwo Nauki i Szkolnictwa WyższegoNarodowe Centrum NaukiMinisterio de Ciencia e InnovaciónNational Institutes of Health18-29https://www.ebi.ac.uk/biostudies/studies/S-EPMC6949598biostudies-literatureUnknown7(Pt 1)<i>Tannerella forsythia</i> is an oral dysbiotic periodontopathogen involved in severe human periodontal disease. As part of its virulence factor armamentarium, at the site of colonization it secretes mirolysin, a metallopeptidase of the unicellular pappalysin family, as a zymogen that is proteolytically auto-activated extracellularly at the Ser54-Arg55 bond. Crystal structures of the catalytically impaired promirolysin point mutant E225A at 1.4 and 1.6 Å revealed that latency is exerted by an N-terminal 34-residue pro-segment that shields the front surface of the 274-residue catalytic domain, thus preventing substrate access. The catalytic domain conforms to the metzincin clan of metallopeptidases and contains a double calcium site, which acts as a calcium switch for activity. The pro-segIUCrJStructure-based mechanism of cysteine-switch latency and of catalysis by pappalysin-family metallopeptidases.PMC69495981306/MOB/IV/2015/0Ksiazek MGuevara TGomis-Ruth FXPotempa JRodriguez-Banqueri AfalseStructure-based mechanism of cysteine-switch latency and of catalysis by pappalysin-family metallopeptidases.<i>Tannerella forsythia</i> is an oral dysbiotic periodontopathogen involved in severe human periodontal disease. As part of its virulence factor armamentarium, at the site of colonization it secretes mirolysin, a metallopeptidase of the unicellular pappalysin family, as a zymogen that is proteolytically auto-activated extracellularly at the Ser54-Arg55 bond. Crystal structures of the catalytically impaired promirolysin point mutant E225A at 1.4 and 1.6 Å revealed that latency is exerted by an N-terminal 34-residue pro-segment that shields the front surface of the 274-residue catalytic domain, thus preventing substrate access. The catalytic domain conforms to the metzincin clan of metallopeptidases and contains a double calcium site, which acts as a calcium switch for activity. The pro-seg2020-01-01T00:00:00Z2020 Jan2025-04-26T14:56:23.903Z2020-05-22T08:27:24ZS-EPMC69495983194990110.1107/S2052252519013848