2vl8

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Current revision (10:01, 9 May 2024) (edit) (undo)
 
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<StructureSection load='2vl8' size='340' side='right'caption='[[2vl8]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
<StructureSection load='2vl8' size='340' side='right'caption='[[2vl8]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[2vl8]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_oedematis_sporogenes"_sordelli_1923 "bacillus oedematis sporogenes" sordelli 1923]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VL8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VL8 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[2vl8]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Paeniclostridium_sordellii Paeniclostridium sordellii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VL8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VL8 FirstGlance]. <br>
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</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=CTS:CASTANOSPERMINE'>CTS</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2vkh|2vkh]], [[2vkd|2vkd]]</div></td></tr>
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<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=CTS:CASTANOSPERMINE'>CTS</scene>, <scene name='pdbligand=UDP:URIDINE-5-DIPHOSPHATE'>UDP</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=2vl8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vl8 OCA], [https://pdbe.org/2vl8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vl8 RCSB], [https://www.ebi.ac.uk/pdbsum/2vl8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vl8 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=2vl8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vl8 OCA], [https://pdbe.org/2vl8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vl8 RCSB], [https://www.ebi.ac.uk/pdbsum/2vl8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vl8 ProSAT]</span></td></tr>
</table>
</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TCSL1_PAESO TCSL1_PAESO] Precursor of a cytotoxin that targets the vascular endothelium, inducing an anti-inflammatory effect and resulting in lethal toxic shock syndrome (PubMed:19527792, PubMed:24919149, PubMed:29146177). TcsL constitutes the main toxin that mediates the pathology of P.sordellii infection, an anaerobic Gram-positive bacterium found in soil and in the gastrointestinal and vaginal tracts of animals and humans; although the majority of carriers are asymptomatic, pathogenic P.sordellii infections arise rapidly and are highly lethal (PubMed:29146177). This form constitutes the precursor of the toxin: it enters into host cells and mediates autoprocessing to release the active toxin (Glucosyltransferase TcsL) into the host cytosol (PubMed:32302524, PubMed:17334356, PubMed:27303685). Targets vascular endothelium by binding to the semaphorin proteins SEMA6A and SEMA6B, and enters host cells via clathrin-mediated endocytosis (PubMed:32302524). Once entered into host cells, acidification in the endosome promotes the membrane insertion of the translocation region and formation of a pore, leading to translocation of the GT44 and peptidase C80 domains across the endosomal membrane (By similarity). This activates the peptidase C80 domain and autocatalytic processing, releasing the N-terminal part (Glucosyltransferase TcsL), which constitutes the active part of the toxin, in the cytosol (PubMed:17334356, PubMed:27303685).[UniProtKB:P18177]<ref>PMID:17334356</ref> <ref>PMID:19527792</ref> <ref>PMID:24919149</ref> <ref>PMID:27303685</ref> <ref>PMID:32302524</ref> <ref>PMID:29146177</ref> Active form of the toxin, which is released into the host cytosol following autoprocessing and inactivates small GTPases (PubMed:8626575, PubMed:8626586, PubMed:9632667, PubMed:17901056, PubMed:19744486, PubMed:24905543, PubMed:24919149, PubMed:27303685, PubMed:27023605, PubMed:30622517). Acts by mediating monoglucosylation of small GTPases of the Ras (H-Ras/HRAS, K-Ras/KRAS, N-Ras/NRAS and Ral/RALA) family in host cells at the conserved threonine residue located in the switch I region ('Thr-37/35'), using UDP-alpha-D-glucose as the sugar donor (PubMed:8858106, PubMed:8626575, PubMed:8626586, PubMed:9632667, PubMed:17901056, PubMed:19744486, PubMed:24905543, PubMed:24919149, PubMed:27023605, PubMed:30622517). Also able to catalyze monoglucosylation of some members of the Rho family (Rac1 and Rap2A), but with less efficiency than with Ras proteins (PubMed:8626586, PubMed:9632667, PubMed:19744486, PubMed:24905543). Monoglucosylation of host small GTPases completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form and leading to apoptosis (PubMed:8626586, PubMed:9632667, PubMed:17910886). Induces an anti-inflammatory effect, mainly by inactivating Ras proteins which results in blockage of the cell cycle and killing of immune cells (PubMed:17910886, PubMed:24919149). The absence or moderate local inflammatory response allows C.sordellii spreading in deep tissues, production of toxin which is released in the general circulation and causes a toxic shock syndrome (PubMed:24919149, PubMed:29146177).<ref>PMID:17901056</ref> <ref>PMID:17910886</ref> <ref>PMID:19744486</ref> <ref>PMID:24905543</ref> <ref>PMID:24919149</ref> <ref>PMID:27023605</ref> <ref>PMID:27303685</ref> <ref>PMID:30622517</ref> <ref>PMID:8626575</ref> <ref>PMID:8626586</ref> <ref>PMID:8858106</ref> <ref>PMID:9632667</ref> <ref>PMID:29146177</ref>
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bacillus oedematis sporogenes sordelli 1923]]
 
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Aktories, K]]
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[[Category: Paeniclostridium sordellii]]
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[[Category: Jank, T]]
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[[Category: Aktories K]]
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[[Category: Schulz, G E]]
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[[Category: Jank T]]
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[[Category: Ziegler, M O.P]]
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[[Category: Schulz GE]]
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[[Category: Glycosyltransferase]]
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[[Category: Ziegler MOP]]
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[[Category: Toxin]]
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Current revision

CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF LETHAL TOXIN FROM CLOSTRIDIUM SORDELLII IN COMPLEX WITH UDP, CASTANOSPERMINE AND CALCIUM ION

PDB ID 2vl8

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