3ti9

Crystal structure of the basic protease BprB from the ovine footrot pathogen, Dichelobacter nodosus

spinqualitylabelsall models 3ti9, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3ti9 is a 1 chain structure with sequence from "fusiformis_nodosus"_beveridge_1941 "fusiformis nodosus" beveridge 1941. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA, CL, GOL Related: 3lpa, 3ti7 Gene: bprB ("Fusiformis nodosus" Beveridge 1941) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The ovine footrot pathogen, Dichelobacter nodosus, secretes three subtilisin-like proteases that play an important role in the pathogenesis of footrot through their ability to mediate tissue destruction. Virulent and benign strains of D. nodosus secrete the basic proteases BprV and BprB, respectively, with the catalytic domain of these enzymes having 96% sequence identity. Currently, it is not known how sequence variation between these two putative virulence factors influences their respective biological activity. We have determined the high-resolution crystal structures of BprV and BprB. These data reveal that that the S1 pocket of BprV is more hydrophobic, but smaller than that of BprB. We show that BprV is more effective in degrading extracellular matrix components of the host tissue than BprB. Mutation of two residues around the S1 pocket of BprB to the equivalent residues in BprV dramatically enhanced its proteolytic activity against elastin substrates. Application of a novel approach for profiling substrate specificity, the Rapid Endopeptidase Profiling Library (REPLi) method, revealed that both enzymes prefer cleaving after hydrophobic residues (and in particular P1 leucine) but that BprV has more restricted primary substrate specificity than BprB. Furthermore, for P1-Leu containing substrates we found that BprV is a significantly more efficient enzyme than BprB. Collectively, these data illuminate how subtle changes in D. nodosus proteases may significantly influence tissue destruction as part of the ovine footrot pathogenesis process. The S1 pocket of a bacterial derived subtilisin-like protease underpins effective tissue destruction.,Wong W, Wijeyewickrema LC, Kennan RM, Reeve SB, Steer DL, Reboul C, Smith AI, Pike RN, Rood JI, Whisstock JC, Porter CJ J Biol Chem. 2011 Oct 11. PMID:21990366 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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