2vk9

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(New page: 200px {{Structure |PDB= 2vk9 |SIZE=350|CAPTION= <scene name='initialview01'>2vk9</scene>, resolution 2.85&Aring; |SITE= |LIGAND= |ACTIVITY= |GENE= }} '''CRYS...)
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[[Image:2vk9.jpg|left|200px]]
 
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{{Structure
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==CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF ALPHA-TOXIN FROM CLOSTRIDIUM NOVYI==
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|PDB= 2vk9 |SIZE=350|CAPTION= <scene name='initialview01'>2vk9</scene>, resolution 2.85&Aring;
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<StructureSection load='2vk9' size='340' side='right'caption='[[2vk9]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND=
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<table><tr><td colspan='2'>[[2vk9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_novyi Clostridium novyi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VK9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VK9 FirstGlance]. <br>
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|ACTIVITY=
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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]] 2.85&#8491;</td></tr>
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|GENE=
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2vk9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vk9 OCA], [https://pdbe.org/2vk9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vk9 RCSB], [https://www.ebi.ac.uk/pdbsum/2vk9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vk9 ProSAT]</span></td></tr>
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}}
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/TCDA_CLONO TCDA_CLONO] Precursor of a cytotoxin, which enters into host cells and mediates autoprocessing to release the active toxin (N-acetylglucosaminyltransferase TcdA) into the host cytosol (By similarity). 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 (N-acetylglucosaminyltransferase TcdA), which constitutes the active part of the toxin, in the cytosol (PubMed:17334356).[UniProtKB:P18177]<ref>PMID:17334356</ref> Active form of the toxin, which is released into the host cytosol following autoprocessing and inactivates small GTPases (PubMed:8810274, PubMed:16157585). Acts by mediating monoglycosylation of small GTPases of the Rho family (Rac1, RhoA, RhoG and Cdc42) in host cells at the conserved threonine residue located in the switch I region ('Thr-37/35'), using UDP-N-acetyl-alpha-D-glucosamine as the sugar donor (PubMed:8810274, PubMed:16157585). Monoglycosylation of host small GTPases completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption and cell death (PubMed:8810274).<ref>PMID:16157585</ref> <ref>PMID:8810274</ref>
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/vk/2vk9_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2vk9 ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The crystal structures of the catalytic fragments of 'lethal toxin' from Clostridium sordellii and of 'alpha-toxin' from Clostridium novyi have been established. Almost half of the residues follow the chain fold of the glycosyl-transferase type A family of enzymes; the other half forms large alpha-helical protrusions that are likely to confer specificity for the respective targeted subgroup of Rho proteins in the cell. In the crystal, the active center of alpha-toxin contained no substrates and was disassembled, whereas that of lethal toxin, which was ligated with the donor substrate UDP-glucose and cofactor Mn2+, was catalytically competent. Surprisingly, the structure of lethal toxin with Ca2+ (instead of Mn2+) at the cofactor position showed a bound donor substrate with a disassembled active center, indicating that the strictly octahedral coordination sphere of Mn2+ is indispensable to the integrity of the enzyme. The homologous structures of alpha-toxin without substrate, distorted lethal toxin with Ca2+ plus donor, active lethal toxin with Mn2+ plus donor and the homologous Clostridium difficile toxin B with a hydrolyzed donor have been lined up to show the geometry of several reaction steps. Interestingly, the structural refinement of one of the three crystallographically independent molecules of Ca2+-ligated lethal toxin resulted in the glucosyl half-chair conformation expected for glycosyl-transferases that retain the anomeric configuration at the C1'' atom. A superposition of six acceptor substrates bound to homologous enzymes yielded the position of the nucleophilic acceptor atom with a deviation of &lt;1 A. The resulting donor-acceptor geometry suggests that the reaction runs as a circular electron transfer in a six-membered ring, which involves the deprotonation of the nucleophile by the beta-phosphoryl group of the donor substrate UDP-glucose.
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'''CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF ALPHA-TOXIN FROM CLOSTRIDIUM NOVYI'''
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Conformational changes and reaction of clostridial glycosylating toxins.,Ziegler MO, Jank T, Aktories K, Schulz GE J Mol Biol. 2008 Apr 11;377(5):1346-56. Epub 2008 Jan 5. PMID:18325534<ref>PMID:18325534</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 2vk9" style="background-color:#fffaf0;"></div>
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==Overview==
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==See Also==
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The crystal structures of the catalytic fragments of 'lethal toxin' from Clostridium sordellii and of 'alpha-toxin' from Clostridium novyi have been established. Almost half of the residues follow the chain fold of the glycosyl-transferase type A family of enzymes; the other half forms large alpha-helical protrusions that are likely to confer specificity for the respective targeted subgroup of Rho proteins in the cell. In the crystal, the active center of alpha-toxin contained no substrates and was disassembled, whereas that of lethal toxin, which was ligated with the donor substrate UDP-glucose and cofactor Mn(2+), was catalytically competent. Surprisingly, the structure of lethal toxin with Ca(2+) (instead of Mn(2+)) at the cofactor position showed a bound donor substrate with a disassembled active center, indicating that the strictly octahedral coordination sphere of Mn(2+) is indispensable to the integrity of the enzyme. The homologous structures of alpha-toxin without substrate, distorted lethal toxin with Ca(2+) plus donor, active lethal toxin with Mn(2+) plus donor and the homologous Clostridium difficile toxin B with a hydrolyzed donor have been lined up to show the geometry of several reaction steps. Interestingly, the structural refinement of one of the three crystallographically independent molecules of Ca(2+)-ligated lethal toxin resulted in the glucosyl half-chair conformation expected for glycosyl-transferases that retain the anomeric configuration at the C1'' atom. A superposition of six acceptor substrates bound to homologous enzymes yielded the position of the nucleophilic acceptor atom with a deviation of &lt;1 A. The resulting donor-acceptor geometry suggests that the reaction runs as a circular electron transfer in a six-membered ring, which involves the deprotonation of the nucleophile by the beta-phosphoryl group of the donor substrate UDP-glucose.
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*[[Hemolysin 3D structures|Hemolysin 3D structures]]
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== References ==
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==About this Structure==
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<references/>
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2VK9 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Clostridium_novyi Clostridium novyi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VK9 OCA].
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__TOC__
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</StructureSection>
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==Reference==
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Conformational Changes and Reaction of Clostridial Glycosylating Toxins., Ziegler MO, Jank T, Aktories K, Schulz GE, J Mol Biol. 2008 Jan 5;. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18325534 18325534]
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[[Category: Clostridium novyi]]
[[Category: Clostridium novyi]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Aktories, K.]]
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[[Category: Aktories K]]
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[[Category: Jank, T.]]
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[[Category: Jank T]]
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[[Category: Schulz, G E.]]
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[[Category: Schulz GE]]
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[[Category: Ziegler, M O.P.]]
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[[Category: Ziegler MOP]]
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[[Category: glycosyltransferase]]
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[[Category: toxin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:47:26 2008''
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Current revision

CRYSTAL STRUCTURE OF THE CATALYTIC DOMAIN OF ALPHA-TOXIN FROM CLOSTRIDIUM NOVYI

PDB ID 2vk9

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