ArticleThe Journal of biological chemistry2010
Proenzyme structure and activation of astacin metallopeptidase.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 92 citations in OpenAlex.
- Crossing the barrier or how regulation of ovastacin controls fertilization and translates into clinical phenotypes.iScience · 2025Review
- NMR structure of emfourin, a novel protein metalloprotease inhibitor: Insights into the mechanism of action.The Journal of biological chemistry · 2023Article
- Article
- Zymogenic latency in an ∼250-million-year-old astacin metallopeptidase.Acta crystallographica. Section D, Structural biology · 2022Article
- Dynamics of the secreted frizzled related protein Sizzled and potential implications for binding to bone morphogenetic protein-1 (BMP-1).Scientific reports · 2022Article
- Structural and evolutionary insights into astacin metallopeptidases.Frontiers in molecular biosciences · 2022Article
- Spodium Bonds in Biological Systems: Expanding the Role of Zn in Protein Structure and Function.Journal of chemical information and modeling · 2021Article
- The Wnt-specific astacin proteinase HAS-7 restricts head organizer formation in Hydra.BMC biology · 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
- Reversible autoinhibitory regulation ofProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Article
- 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
- The structure ofThe Journal of biological chemistry · 2019Article
- Structure of mammalian plasma fetuin-B and its mechanism of selective metallopeptidase inhibition.IUCrJ · 2019Article
- Design and Production of a Recombinant Hybrid Toxin to Raise Protective Antibodies AgainstToxins · 2019Article
- Functional and structural studies of tolloid-like 1 mutants associated with atrial-septal defect 6.Bioscience reports · 2019Article
- Mammalian plasma fetuin-B is a selective inhibitor of ovastacin and meprin metalloproteinases.Scientific reports · 2019Article
- Glycan-Independent Gamete Recognition Triggers Egg Zinc Sparks and ZP2 Cleavage to Prevent Polyspermy.Developmental cell · 2018Article
- De novo metatranscriptome assembly and coral gene expression profile of Montipora capitata with growth anomaly.BMC genomics · 2017Article
- Intracellular activation of ovastacin mediates pre-fertilization hardening of the zona pellucida.Molecular human reproduction · 2017Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteolysis is regulated by inactive (latent) zymogens, with a prosegment preventing access of substrates to the active-site cleft of the enzyme. How latency is maintained often depends on the catalytic mechanism of the protease. For example, in several families of the metzincin metallopeptidases, a "cysteine switch" mechanism involves a conserved prosegment motif with a cysteine residue that coordinates the catalytic zinc ion. Another family of metzincins, the astacins, do not possess a cysteine switch, so latency is maintained by other means. We have solved the high resolution crystal structure of proastacin from the European crayfish, Astacus astacus. Its prosegment is the shortest structurally reported for a metallopeptidase, and it has a unique structure. It runs through the active-site cleft in reverse orientation to a genuine substrate. Moreover, a conserved aspartate, projected by a wide loop of the prosegment, coordinates the zinc ion instead of the catalytic solvent molecule found in the mature enzyme. Activation occurs through two-step limited proteolysis and entails major rearrangement of a flexible activation domain, which becomes rigid and creates the base of the substrate-binding cleft. Maturation also requires the newly formed N terminus to be precisely trimmed so that it can participate in a buried solvent-mediated hydrogen-bonding network, which includes an invariant active-site residue. We describe a novel mechanism for latency and activation, which shares some common features both with other metallopeptidases and with serine peptidases.
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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.