ArticleThe Journal of biological chemistry2013
Substrate cleavage profiling suggests a distinct function of Bacteroides fragilis metalloproteinases (fragilysin and metalloproteinase II) at the microbiome-inflammation-cancer interface.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- mRNA Display for Identifying Peptide Substrates of Enzymes.Biochemistry · 2026Review
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- Comprehensive 16s rRNA sequencing and metabolomics to investigate the effect of anticancer bioactive peptides combined with oxaliplatin on gastric cancer.Scientific reports · 2026Article
- Microbiome dysbiosis and its modulation in cancer development, prevention and therapy.Frontiers in oncology · 2026Review
- The Enteric Microbiome in Early-Onset Colorectal Cancer: A Comprehensive Review of Its Role as a Biomarker of Disease.Clinical and translational gastroenterology · 2025Review
- Modeling ETBF-Mediated Colorectal Tumorigenesis Using AOM/DSS in Wild-Type Mice.International journal of molecular sciences · 2025Article
- Gut microbiota therapy in gastrointestinal diseases.Frontiers in cell and developmental biology · 2025Review
- The dynamic crosslinking between gut microbiota and inflammation during aging: reviewing the nutritional and hormetic approaches against dysbiosis and inflammaging.Biogerontology · 2024Review
- PepSeq: a fully in vitro platform for highly multiplexed serology using customizable DNA-barcoded peptide libraries.Nature protocols · 2023Review
- Colorectal cancer: The epigenetic role of microbiome.World journal of clinical cases · 2019Review
- The association of diet, gut microbiota and colorectal cancer: what we eat may imply what we get.Protein & cell · 2018Review
- Article
- Aspects of Gut Microbiota and Immune System Interactions in Infectious Diseases, Immunopathology, and Cancer.Frontiers in immunology · 2018Review
- Next-generation probiotics: the spectrum from probiotics to live biotherapeutics.Nature microbiology · 2017Article
- Article
- Structural Change in Microbiota by a Probiotic Cocktail Enhances the Gut Barrier and Reduces Cancer via TLR2 Signaling in a Rat Model of Colon Cancer.Digestive diseases and sciences · 2016Article
- 16S rRNA amplicon sequencing identifies microbiota associated with oral cancer, human papilloma virus infection and surgical treatment.Oncotarget · 2016Article
- High-Throughput Multiplexed Peptide-Centric Profiling Illustrates Both Substrate Cleavage Redundancy and Specificity in the MMP Family.Chemistry & biology · 2015Article
- CleavPredict: A Platform for Reasoning about Matrix Metalloproteinases Proteolytic Events.PloS one · 2015Article
- Peptide Sequence Region That is Essential for the Interactions of the Enterotoxigenic Bacteroides fragilis Metalloproteinase II with E-cadherin.Journal of proteolysis · 2014Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Enterotoxigenic anaerobic Bacteroides fragilis is a significant source of inflammatory diarrheal disease and a risk factor for colorectal cancer. Two distinct metalloproteinase types (the homologous 1, 2, and 3 isoforms of fragilysin (FRA1, FRA2, and FRA3, respectively) and metalloproteinase II (MPII)) are encoded by the B. fragilis pathogenicity island. FRA was demonstrated to be important to pathogenesis, whereas MPII, also a potential virulence protein, remained completely uncharacterized. Here, we, for the first time, extensively characterized MPII in comparison with FRA3, a representative of the FRA isoforms. We employed a series of multiplexed peptide cleavage assays to determine substrate specificity and proteolytic characteristics of MPII and FRA. These results enabled implementation of an efficient assay of MPII activity using a fluorescence-quenched peptide and contributed to structural evidence for the distinct substrate cleavage preferences of MPII and FRA. Our data imply that MPII specificity mimics the dibasic Arg↓Arg cleavage motif of furin-like proprotein convertases, whereas the cleavage motif of FRA (Pro-X-X-Leu-(Arg/Ala/Leu)↓) resembles that of human matrix metalloproteinases. To the best of our knowledge, MPII is the first zinc metalloproteinase with the dibasic cleavage preferences, suggesting a high level of versatility of metalloproteinase proteolysis. Based on these data, we now suggest that the combined (rather than individual) activity of MPII and FRA is required for the overall B. fragilis virulence in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.