8ehc

Structure of Tannerella forsythia selenomethionine-derivatized potempin E

spinqualitylabelsall models 8ehc, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8ehc 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 2Å Ligands: GOL, MSE Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A1D3UL35_TANFO Publication Abstract from PubMed Periodontopathogenic Tannerella forsythia uniquely secretes six peptidases of disparate catalytic classes and families that operate as virulence factors during infection of the gums, the KLIKK-peptidases. Their coding genes are immediately downstream of novel ORFs encoding the 98-132 residue potempins (Pot) A, B1, B2, C, D and E. These are outer-membrane-anchored lipoproteins that specifically and potently inhibit the respective downstream peptidase through stable complexes that protect the outer membrane of T. forsythia, as shown in vivo. Remarkably, PotA also contributes to bacterial fitness in vivo and specifically inhibits matrix metallopeptidase (MMP) 12, a major defence component of oral macrophages, thus featuring a novel and highly-specific physiological MMP inhibitor. Information from 11 structures and high-confidence homology models showed that the potempins are distinct beta-barrels with either a five-stranded OB-fold (PotA, PotC and PotD) or an eight-stranded up-and-down fold (PotE, PotB1 and PotB2), which are novel for peptidase inhibitors. Particular loops insert like wedges into the active-site cleft of the genetically-linked peptidases to specifically block them either via a new "bilobal" or the classic "standard" mechanism of inhibition. These results discover a unique, tightly-regulated proteolytic armamentarium for virulence and competence, the KLIKK-peptidase/potempin system. A unique network of attack, defence and competence on the outer membrane of the periodontitis pathogen Tannerella forsythia.,Ksiazek M, Goulas T, Mizgalska D, Rodriguez-Banqueri A, Eckhard U, Veillard F, Waligorska I, Benedyk-Machaczka M, Sochaj-Gregorczyk AM, Madej M, Thogersen IB, Enghild JJ, Cuppari A, Arolas JL, de Diego I, Lopez-Pelegrin M, Garcia-Ferrer I, Guevara T, Dive V, Zani ML, Moreau T, Potempa J, Gomis-Ruth FX Chem Sci. 2022 Dec 12;14(4):869-888. doi: 10.1039/d2sc04166a. eCollection 2023 , Jan 25. PMID:36755705 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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