7od0

Mirolysin in complex with compound 9

spinqualitylabelsall models 7od0, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7od0 is a 6 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 2.1Å Ligands: ACT, CA, CL, EDO, V7Q, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A0F7IPS1_TANFO Publication Abstract from PubMed Mirolysin is a secretory protease of Tannerella forsythia, a member of the dysbiotic oral microbiota responsible for periodontitis. In this study, we show that mirolysin latency is achieved by a "cysteine-switch" mechanism exerted by Cys23 in the N-terminal profragment. Mutation of Cys23 shortened the time needed for activation of the zymogen from several days to 5 min. The mutation also decreased the thermal stability and autoproteolysis resistance of promirolysin. Mature mirolysin is a thermophilic enzyme and shows optimal activity at 65 degrees C. Through NMR-based fragment screening, we identified a small molecule (compound (cpd) 9) that blocks promirolysin maturation and functions as a competitive inhibitor (Ki = 3.2 microM), binding to the S1' subsite of the substrate-binding pocket. Cpd 9 shows superior specificity and does not interact with other T. forsythia proteases or Lys/Arg-specific proteases. Latency, thermal stability, and identification of an inhibitory compound of mirolysin, a secretory protease of the human periodontopathogen Tannerella forsythia.,Zak KM, Bostock MJ, Waligorska I, Thogersen IB, Enghild JJ, Popowicz GM, Grudnik P, Potempa J, Ksiazek M J Enzyme Inhib Med Chem. 2021 Dec;36(1):1267-1281. doi:, 10.1080/14756366.2021.1937619. PMID:34210221 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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