10.4225/03/57428C1393E72 RM Kennan W Wong O Dhungyel X Han D Wong D Parker CJ Rosado Ruby Law Sheena McGowan SB Reeve V Levina GA Powers RN Pike SP Bottomley AI Smith I Marsh RJ Whittington James Whisstock Christopher Porter JI Rood Virulence-associated subtilisin-like proteases that use a novel disulphide-tethered exosite to mediate substrate specificity (3LPA, 3LPC, 3LPD) 2016 Monash University Peptide Hydrolases Endopeptidases ImagingLocus 2016-12-11 22:35:17 article https://bridges.monash.edu/articles/Virulence-associated_subtilisin-like_proteases_that_use_a_novel_disulphide-tethered_exosite_to_mediate_substrate_specificity_3LPA_3LPC_3LPD_/3122968 <div>Many bacterial pathogens produce extracellular proteases that are involved in the degradation of the host extracellular matrix. Dichelobacter nodosus, which causes ovine footrot, is one such pathogen, Mutagenesis and virulence studies revealed that AprV2, one of three secreted subtilisin-like D.¬†nodosus proteases, is required for virulence. Our work challenges the previous hypothesis that the elastase activity of AprV2 is important for disease progression, since aprV2 mutants were virulent when complemented with a variant with impaired elastase activity. These data reveal that an unusual extended disulphide-tethered loop functions as an exosite that governs the ability of AprV2 to degrade insoluble extracellular matrix components. The disulphide bond and Tyr92, located at the exposed end of the loop, were functionally important. Bioinformatics suggests that other pathogens utilize a similar mechanism, providing a new paradigm for understanding the role of proteases in disease.</div><div><br></div><p></p>