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Structural and functional diversity of metalloproteinases encoded by the Bacteroides fragilis pathogenicity island
Author(s) -
Shiryaev Sergey A.,
Aleshin Alexander E.,
Muranaka Norihito,
Kukreja Muskan,
Routenberg David A.,
Remacle Albert G.,
Liddington Robert C.,
Cieplak Piotr,
Kozlov Igor A.,
Strongin Alex Y.
Publication year - 2014
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12804
Subject(s) - bacteroides fragilis , virulence , biology , pathogenicity island , cleavage (geology) , proteases , isozyme , pathogenicity , microbiology and biotechnology , protease , gene isoform , matrix metalloproteinase , genetics , enzyme , bacteria , gene , biochemistry , paleontology , fracture (geology)
Bacteroides fragilis causes the majority of anaerobic infections in humans. The presence of a pathogenicity island in the genome discriminates pathogenic and commensal B. fragilis strains. The island encodes metalloproteinase II ( MPII ), a potential virulence protein, and one of three homologous fragilysin isozymes ( FRA ; also termed B. fragilis toxin or BFT ). Here, we report biochemical data on the structural–functional characteristics of the B. fragilis pathogenicity island proteases by reporting the crystal structure of MPII at 2.13 Å resolution, combined with detailed characterization of the cleavage preferences of MPII and FRA 3 (as a representative of the FRA isoforms), identified using a high‐throughput peptide cleavage assay with 18 583 substrate peptides. We suggest that the evolution of the MPII catalytic domain can be traced to human and archaebacterial proteinases, whereas the prodomain fold is a feature specific to MPII and FRA . We conclude that the catalytic domain of both MPII and FRA 3 evolved differently relative to the prodomain, and that the prodomain evolved specifically to fit the B. fragilis pathogenicity. Overall, our data provide insights into the evolution of cleavage specificity and activation mechanisms in the virulent metalloproteinases.