4ON1

Crystal Structure of metalloproteinase-II from Bacteroides fragilis

4ON1 の概要

• エントリーDOI: 10.2210/pdb4on1/pdb
• 分子名称: Putative metalloprotease II, ZINC ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: pathogenicity island, human pathogen, fragilysin, metalloproteinases, extracellular, hydrolase
• 由来する生物種: Bacteroides fragilis
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 85065.40

構造登録者

Aleshin, A.E.,Liddington, R.C.,Shiryaev, S.A.,Strongin, A.Y. (登録日: 2014-01-28, 公開日: 2014-04-09, 最終更新日: 2024-02-28)

主引用文献

Shiryaev, S.A.,Aleshin, A.E.,Muranaka, N.,Kukreja, M.,Routenberg, D.A.,Remacle, A.G.,Liddington, R.C.,Cieplak, P.,Kozlov, I.A.,Strongin, A.Y.
Structural and functional diversity of metalloproteinases encoded by the Bacteroides fragilis pathogenicity island.
Febs J., 281:2487-2502, 2014

PubMed Abstract: 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 FRA3 (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 FRA3 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.

PubMed: 24698179
DOI: 10.1111/febs.12804

実験手法

X-RAY DIFFRACTION (2.13 Å)