6r7u | pdb_00006r7u

Selenomethionine variant of Tannerella forsythia promirolysin mutant E225A

spinqualitylabelsall models 6r7u, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6r7u is a 2 chain structure with sequence from Tannerella forsythia. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.6Å Ligands: BO3, CA, CSX, GOL, MSE, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function G8ULV1_TANFA Publication Abstract from PubMed Tannerella forsythia is an oral dysbiotic periodontopathogen involved in severe human periodontal disease. As part of its virulence factor armamentarium, at the site of colonization it secretes mirolysin, a metallopeptidase of the unicellular pappalysin family, as a zymogen that is proteolytically auto-activated extracellularly at the Ser54-Arg55 bond. Crystal structures of the catalytically impaired promirolysin point mutant E225A at 1.4 and 1.6 A revealed that latency is exerted by an N-terminal 34-residue pro-segment that shields the front surface of the 274-residue catalytic domain, thus preventing substrate access. The catalytic domain conforms to the metzincin clan of metallopeptidases and contains a double calcium site, which acts as a calcium switch for activity. The pro-segment traverses the active-site cleft in the opposite direction to the substrate, which precludes its cleavage. It is anchored to the mature enzyme through residue Arg21, which intrudes into the specificity pocket in cleft sub-site S1'. Moreover, residue Cys23 within a conserved cysteine-glycine motif blocks the catalytic zinc ion by a cysteine-switch mechanism, first described for mammalian matrix metallopeptidases. In addition, a 1.5 A structure was obtained for a complex of mature mirolysin and a tetradecapeptide, which filled the cleft from sub-site S1' to S6'. A citrate molecule in S1 completed a product-complex mimic that unveiled the mechanism of substrate binding and cleavage by mirolysin, the catalytic domain of which was already preformed in the zymogen. These results, including a preference for cleavage before basic residues, are likely to be valid for other unicellular pappalysins derived from archaea, bacteria, cyanobacteria, algae and fungi, including archetypal ulilysin from Methanosarcina acetivorans. They may further apply, at least in part, to the multi-domain orthologues of higher organisms. Structure-based mechanism of cysteine-switch latency and of catalysis by pappalysin-family metallopeptidases.,Guevara T, Rodriguez-Banqueri A, Ksiazek M, Potempa J, Gomis-Ruth FX IUCrJ. 2020 Jan 1;7(Pt 1):18-29. doi: 10.1107/S2052252519013848. eCollection 2020, Jan 1. PMID:31949901 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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