Virulence-associated subtilisin-like proteases that use a novel disulphide-tethered exosite to mediate substrate specificity (3LPA, 3LPC, 3LPD)
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
10.4225/03/57428C1393E72
https://bridges.monash.edu/articles/dataset/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>
2016-12-11 22:35:17
Peptide Hydrolases
Endopeptidases
ImagingLocus
Molecular Biology
Biochemistry