8b2n: Difference between revisions
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==Potempin A (PotA) from Tannerella forsythia in complex with the catalytic domain of human MMP-12== | |||
<StructureSection load='8b2n' size='340' side='right'caption='[[8b2n]], [[Resolution|resolution]] 1.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8b2n]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Tannerella_forsythia Tannerella forsythia]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8B2N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8B2N FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8b2n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8b2n OCA], [https://pdbe.org/8b2n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8b2n RCSB], [https://www.ebi.ac.uk/pdbsum/8b2n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8b2n ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:36755705</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[ | </div> | ||
[[Category: | <div class="pdbe-citations 8b2n" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: | ==See Also== | ||
[[Category: | *[[Matrix metalloproteinase 3D structures|Matrix metalloproteinase 3D structures]] | ||
[[Category: Cuppari | == References == | ||
[[Category: | <references/> | ||
[[Category: Guevara | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | |||
[[Category: Tannerella forsythia]] | |||
[[Category: Arolas JL]] | |||
[[Category: Cuppari A]] | |||
[[Category: Garcia-Ferrer I]] | |||
[[Category: Goulas T]] | |||
[[Category: Guevara T]] | |||
[[Category: Ksiazek M]] | |||
[[Category: Lopez-Pelegrin M]] | |||
[[Category: Potempa J]] | |||
[[Category: Rodriguez-Banqueri A]] | |||
Latest revision as of 12:28, 17 October 2024
Potempin A (PotA) from Tannerella forsythia in complex with the catalytic domain of human MMP-12Potempin A (PotA) from Tannerella forsythia in complex with the catalytic domain of human MMP-12
Structural highlights
Publication Abstract from PubMedPeriodontopathogenic 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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