Virulence-associated subtilisin-like proteases that use a novel disulphide-tethered exosite to mediate substrate specificity (3LPA, 3LPC, 3LPD)

Authors:
Kennan R.M., Wong W., Dhungyel O., Han X., Wong D., Parker D., Rosado C.J., Law R.H.P., McGowan S., Reeve S.B., Levina V., Powers G.A., Pike R.N., Bottomley S.P., Smith A.I., Marsh I., Whittington R.J., Whisstock J.C., Porter C.J., Rood J.I.

Abstract:

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.

PDB id(s): 3LPA, 3LPC, 3LPD

Persistent Handle: 102.100.100/4382

Institution: Monash University

Dataset Information:

  • Datasets: 6
  • Files: 1624

Experiment Last Updated: 25th November 2010 19:18

DATASET 1
Dataset Description: AprV2
Dataset Metadata: [Hide]
  • Resolution Limit: 2.0 Å
  • Diffractometer Type: Rotating Anode
  • X-Ray Source: RIGAKU RAXIS IV
  • Crystal Name: AprV2
Data Files (446): [Show]
DATASET 2
Dataset Description: AprB2
Dataset Metadata: [Hide]
  • Resolution Limit: 1.7 Å
  • Diffractometer Type: Rotating Anode
  • X-Ray Source: RIGAKU RAXIS IV
  • Crystal Name: AprB2
Data Files (799): [Show]
DATASET 3
Dataset Description: AprV2.C141S
Dataset Metadata: [Hide]
  • Resolution Limit: 2.1 Å
  • Diffractometer Type: Rotating Anode
  • X-Ray Source: RIGAKU RAXIS IV
  • Crystal Name: AprV2.C141S
Data Files (364): [Show]
DATASET 4
Dataset Description: AprV2
Data Files (5): [Show]
DATASET 5
Dataset Description: AprB2
Data Files (5): [Show]
DATASET 6
Dataset Description: AprV2.C141S
Data Files (5): [Show]