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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[4dny]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DNY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DNY FirstGlance]. <br> | | <table><tr><td colspan='2'>[[4dny]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_O157:H7 Escherichia coli O157:H7]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DNY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DNY FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.61Å</td></tr> |
| | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=IOD:IODIDE+ION'>IOD</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=4dny FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dny OCA], [https://pdbe.org/4dny PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dny RCSB], [https://www.ebi.ac.uk/pdbsum/4dny PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dny ProSAT]</span></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=4dny FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dny OCA], [https://pdbe.org/4dny PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dny RCSB], [https://www.ebi.ac.uk/pdbsum/4dny PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dny ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/STCE_ECO57 STCE_ECO57]] Virulence factor that contributes to intimate adherence of enterohemorrhagic E.coli (EHEC) O157:H7 to host cells. Is able to cleave the secreted human mucin 7 (MUC7) and the glycoprotein 340 (DMBT1/GP340). Also cleaves human C1 inhibitor (SERPING1), a regulator of multiple inflammatory pathways, and binds and localizes it to bacterial and host cell surfaces, protecting them from complement-mediated lysis. Therefore, the current model proposes two roles for StcE during infection: it acts first as a mucinase, allowing passage of EHEC through the oral cavity by cleaving the salivary glycoproteins that are responsible for bacterial aggregation. Similarly, in the colon, StcE cleaves the glycoproteins that protect the intestinal epithelial surface, allowing EHEC to come into close contact with host cell membranes. Secondly, it acts as an anti-inflammatory agent by localizing SERPING1 to cell membranes.<ref>PMID:15731026</ref> <ref>PMID:12123444</ref> <ref>PMID:15096536</ref> <ref>PMID:16788173</ref>
| + | [https://www.uniprot.org/uniprot/STCE_ECO57 STCE_ECO57] Virulence factor that contributes to intimate adherence of enterohemorrhagic E.coli (EHEC) O157:H7 to host cells. Is able to cleave the secreted human mucin 7 (MUC7) and the glycoprotein 340 (DMBT1/GP340). Also cleaves human C1 inhibitor (SERPING1), a regulator of multiple inflammatory pathways, and binds and localizes it to bacterial and host cell surfaces, protecting them from complement-mediated lysis. Therefore, the current model proposes two roles for StcE during infection: it acts first as a mucinase, allowing passage of EHEC through the oral cavity by cleaving the salivary glycoproteins that are responsible for bacterial aggregation. Similarly, in the colon, StcE cleaves the glycoproteins that protect the intestinal epithelial surface, allowing EHEC to come into close contact with host cell membranes. Secondly, it acts as an anti-inflammatory agent by localizing SERPING1 to cell membranes.<ref>PMID:15731026</ref> <ref>PMID:12123444</ref> <ref>PMID:15096536</ref> <ref>PMID:16788173</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Mucin glycoproteins with large numbers of O-linked glycosylations comprise the mucosal barrier lining the mammalian gastrointestinal tract from mouth to gut. A critical biological function of mucins is to protect the underlying epithelium from infection. Enterohemorrhagic Escherichia coli (EHEC), the mediator of severe food- and water-borne disease, can breach this barrier and adhere to intestinal cells. StcE, a approximately 100 kDa metalloprotease secreted by EHEC, plays a pivotal role in remodeling the mucosal lining during infection. To obtain mechanistic insight into its function, we have determined the structure of StcE. Our data reveal a dynamic, multidomain architecture featuring an unusually large substrate-binding cleft and a prominent polarized surface charge distribution highly suggestive of an electrostatic role in substrate targeting. The observation of key conserved motifs in the active site allows us to propose the structural basis for the specific recognition of alpha-O-glycan-containing substrates. Complementary biochemical analysis provides further insight into its distinct substrate specificity and binding stoichiometry.
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| - | Structural insight into the bacterial mucinase StcE essential to adhesion and immune evasion during enterohemorrhagic E. coli infection.,Yu AC, Worrall LJ, Strynadka NC Structure. 2012 Apr 4;20(4):707-17. Epub 2012 Apr 3. PMID:22483117<ref>PMID:22483117</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 4dny" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| Structural highlights
Function
STCE_ECO57 Virulence factor that contributes to intimate adherence of enterohemorrhagic E.coli (EHEC) O157:H7 to host cells. Is able to cleave the secreted human mucin 7 (MUC7) and the glycoprotein 340 (DMBT1/GP340). Also cleaves human C1 inhibitor (SERPING1), a regulator of multiple inflammatory pathways, and binds and localizes it to bacterial and host cell surfaces, protecting them from complement-mediated lysis. Therefore, the current model proposes two roles for StcE during infection: it acts first as a mucinase, allowing passage of EHEC through the oral cavity by cleaving the salivary glycoproteins that are responsible for bacterial aggregation. Similarly, in the colon, StcE cleaves the glycoproteins that protect the intestinal epithelial surface, allowing EHEC to come into close contact with host cell membranes. Secondly, it acts as an anti-inflammatory agent by localizing SERPING1 to cell membranes.[1] [2] [3] [4]
References
- ↑ Grys TE, Siegel MB, Lathem WW, Welch RA. The StcE protease contributes to intimate adherence of enterohemorrhagic Escherichia coli O157:H7 to host cells. Infect Immun. 2005 Mar;73(3):1295-303. PMID:15731026 doi:http://dx.doi.org/10.1128/IAI.73.3.1295-1303.2005
- ↑ Lathem WW, Grys TE, Witowski SE, Torres AG, Kaper JB, Tarr PI, Welch RA. StcE, a metalloprotease secreted by Escherichia coli O157:H7, specifically cleaves C1 esterase inhibitor. Mol Microbiol. 2002 Jul;45(2):277-88. PMID:12123444
- ↑ Lathem WW, Bergsbaken T, Welch RA. Potentiation of C1 esterase inhibitor by StcE, a metalloprotease secreted by Escherichia coli O157:H7. J Exp Med. 2004 Apr 19;199(8):1077-87. PMID:15096536 doi:http://dx.doi.org/10.1084/jem.20030255
- ↑ Grys TE, Walters LL, Welch RA. Characterization of the StcE protease activity of Escherichia coli O157:H7. J Bacteriol. 2006 Jul;188(13):4646-53. PMID:16788173 doi:http://dx.doi.org/10.1128/JB.01806-05
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