ArticleMolecular & cellular proteomics : MCP2011
Proteomic analyses reveal an acidic prime side specificity for the astacin metalloprotease family reflected by physiological substrates.
Article in Molecular & cellular proteomics : MCP, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 145 citations in OpenAlex.
- Serum meprin α levels for the detection of systemic inflammatory response syndrome.Molecular medicine (Cambridge, Mass.) · 2026Article
- Crossing the barrier or how regulation of ovastacin controls fertilization and translates into clinical phenotypes.iScience · 2025Review
- Meprin β Modulates Brevican Proteolysis Impairing Neural Plasticity and Memory Formation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- HYTANE-Identified Latrophilin-3 Cleavage by Meprin β Leads to Loss of the Interaction Domains.Journal of proteome research · 2025Article
- Targeted approach to determine the impact of cancer-associated protease variants.Science advances · 2025Article
- ThePolymers · 2024Review
- Synthesis and structure-activity relationships of pyrazole-based inhibitors of meprin α and β.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Proteolytic processing of galectin-3 by meprin metalloproteases is crucial for host-microbiome homeostasis.Science advances · 2023Article
- Zymogenic latency in an ∼250-million-year-old astacin metallopeptidase.Acta crystallographica. Section D, Structural biology · 2022Article
- Helical ultrastructure of the metalloprotease meprin α in complex with a small molecule inhibitor.Nature communications · 2022Article
- Distinct contributions of meprins to skin regeneration after injury - Meprin α a physiological processer of pro-collagen VII.Matrix biology plus · 2021Article
- The Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra.BMC biology · 2021Article
- Structure and Dynamics of Meprin β in Complex with a Hydroxamate-Based Inhibitor.International journal of molecular sciences · 2021Article
- The crystal structure of a 250-kDa heterotetrameric particle explains inhibition of sheddase meprin β by endogenous fetuin-B.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Cell Surface Processing of CD109 by Meprin β Leads to the Release of Soluble Fragments and Reduced Expression on Extracellular Vesicles.Frontiers in cell and developmental biology · 2021Article
- A Primary Evaluation of Potential Small-Molecule Inhibitors of the Astacin Metalloproteinase Ovastacin, a Novel Drug Target in Female Infertility Treatment.ChemMedChem · 2020Article
- A Pilot Integrative Analysis of Colonic Gene Expression, Gut Microbiota, and Immune Infiltration in Primary Sclerosing Cholangitis-Inflammatory Bowel Disease: Association of Disease With Bile Acid Pathways.Journal of Crohn's & colitis · 2020Article
- Proteolytic profile of larval developmental stages of Penaeus vannamei: An activity and mRNA expression approach.PloS one · 2020Article
- Meprin β induces activities of A disintegrin and metalloproteinases 9, 10, and 17 by specific prodomain cleavage.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- The C-terminal region of human plasma fetuin-B is dispensable for the raised-elephant-trunk mechanism of inhibition of astacin metallopeptidases.Scientific reports · 2019Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Astacins are secreted and membrane-bound metalloproteases with clear associations to many important pathological and physiological processes. Yet with only a few substrates described their biological roles are enigmatic. Moreover, the lack of knowledge of astacin cleavage site specificities hampers assay and drug development. Using PICS (proteomic identification of protease cleavage site specificity) and TAILS (terminal amine isotopic labeling of substrates) degradomics approaches >3000 cleavage sites were proteomically identified for five different astacins. Such broad coverage enables family-wide determination of specificities N- and C-terminal to the scissile peptide bond. Remarkably, meprin α, meprin β, and LAST_MAM proteases exhibit a strong preference for aspartate in the peptide (P)1' position because of a conserved positively charged residue in the active cleft subsite (S)1'. This unparalleled specificity has not been found for other families of extracellular proteases. Interestingly, cleavage specificity is also strongly influenced by proline in P2' or P3' leading to a rare example of subsite cooperativity. This specificity characterizes the astacins as unique contributors to extracellular proteolysis that is corroborated by known cleavage sites in procollagen I+III, VEGF (vascular endothelial growth factor)-A, IL (interleukin)-1β, and pro-kallikrein 7. Indeed, cleavage sites in VEGF-A and pro-kallikrein 7 identified by terminal amine isotopic labeling of substrates matched those reported by Edman degradation. Moreover, the novel substrate FGF-19 was validated biochemically and shown to exhibit altered biological activity after meprin processing.
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