|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Catalytic fragment of cholix toxin from vibrio cholerae in complex with inhibitor V30== | | ==Catalytic fragment of cholix toxin from vibrio cholerae in complex with inhibitor V30== |
| - | <StructureSection load='3ny6' size='340' side='right' caption='[[3ny6]], [[Resolution|resolution]] 1.68Å' scene=''> | + | <StructureSection load='3ny6' size='340' side='right'caption='[[3ny6]], [[Resolution|resolution]] 1.68Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ny6]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillo_virgola_del_koch"_trevisan_1884 "bacillo virgola del koch" trevisan 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NY6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NY6 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ny6]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Vibrio_cholerae Vibrio cholerae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NY6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NY6 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=V30:2-[(5,6-DIMETHYL-4-OXO-3,4-DIHYDROTHIENO[2,3-D]PYRIMIDIN-2-YL)SULFANYL]-N-(2-HYDROXYETHYL)ACETAMIDE'>V30</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]] 1.68Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2q6m|2q6m]], [[3ess|3ess]], [[3ki0|3ki0]], [[3ki1|3ki1]], [[3ki2|3ki2]], [[3ki3|3ki3]], [[3ki4|3ki4]], [[3ki5|3ki5]], [[3ki6|3ki6]], [[3ki7|3ki7]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene>, <scene name='pdbligand=V30:2-[(5,6-DIMETHYL-4-OXO-3,4-DIHYDROTHIENO[2,3-D]PYRIMIDIN-2-YL)SULFANYL]-N-(2-HYDROXYETHYL)ACETAMIDE'>V30</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">chxa, toxA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=666 "Bacillo virgola del Koch" Trevisan 1884])</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=3ny6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ny6 OCA], [https://pdbe.org/3ny6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ny6 RCSB], [https://www.ebi.ac.uk/pdbsum/3ny6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ny6 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)--diphthamide_ADP-ribosyltransferase NAD(+)--diphthamide ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.36 2.4.2.36] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ny6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ny6 OCA], [http://pdbe.org/3ny6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3ny6 RCSB], [http://www.ebi.ac.uk/pdbsum/3ny6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3ny6 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CHXA_VIBCL CHXA_VIBCL]] An NAD-dependent ADP-ribosyltransferase (ADPRT), it catalyzes the transfer of the ADP-ribosyl moiety of oxidized NAD onto eukaryotic elongation factor 2 (eEF-2) thus arresting protein synthesis. It probably uses the eukaryotic prolow-density lipoprotein receptor-related protein 1 (LRP1) to enter mouse cells, although there seems to be at least one other receptor as well. Is active against mouse fibroblasts, Chinese hamster ovary eEF-2, brine shrimp (Artemia spp. nauplii) and upon expression in S.cerevisiae.<ref>PMID:18276581</ref> <ref>PMID:19793133</ref> | + | [https://www.uniprot.org/uniprot/CHXA_VIBCL CHXA_VIBCL] An NAD-dependent ADP-ribosyltransferase (ADPRT), it catalyzes the transfer of the ADP-ribosyl moiety of oxidized NAD onto eukaryotic elongation factor 2 (eEF-2) thus arresting protein synthesis. It probably uses the eukaryotic prolow-density lipoprotein receptor-related protein 1 (LRP1) to enter mouse cells, although there seems to be at least one other receptor as well. Is active against mouse fibroblasts, Chinese hamster ovary eEF-2, brine shrimp (Artemia spp. nauplii) and upon expression in S.cerevisiae.<ref>PMID:18276581</ref> <ref>PMID:19793133</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 23: |
Line 21: |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Exotoxin|Exotoxin]] | + | *[[Exotoxin 3D structures|Exotoxin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Bacillo virgola del koch trevisan 1884]] | + | [[Category: Large Structures]] |
| - | [[Category: Jorgensen, R]] | + | [[Category: Vibrio cholerae]] |
| - | [[Category: Merrill, A R]] | + | [[Category: Jorgensen R]] |
| - | [[Category: Adp-ribosyl transferase]] | + | [[Category: Merrill AR]] |
| - | [[Category: Alpha-beta complex]]
| + | |
| - | [[Category: Nad+ binding]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Transferase-transferase inhibitor complex]]
| + | |
| Structural highlights
Function
CHXA_VIBCL An NAD-dependent ADP-ribosyltransferase (ADPRT), it catalyzes the transfer of the ADP-ribosyl moiety of oxidized NAD onto eukaryotic elongation factor 2 (eEF-2) thus arresting protein synthesis. It probably uses the eukaryotic prolow-density lipoprotein receptor-related protein 1 (LRP1) to enter mouse cells, although there seems to be at least one other receptor as well. Is active against mouse fibroblasts, Chinese hamster ovary eEF-2, brine shrimp (Artemia spp. nauplii) and upon expression in S.cerevisiae.[1] [2]
Publication Abstract from PubMed
The mono-ADP-ribosyltransferase toxins are bacterial virulence factors that contribute to many disease states in plants, animals and humans. These toxins function as enzymes that target various host proteins and covalently attach an ADP-ribose moiety that alters target protein function. We tested compounds from a virtual screen of commercially available compounds combined with a directed PARP inhibitor library and found several compounds that bind tightly and inhibit toxins from Pseudomonas aeruginosa and Vibrio cholerae. The most efficacious compounds completely protected human lung epithelial cells against the cytotoxicity of these bacterial virulence factors. Moreover, we determined high-resolution crystal structures of the best inhibitors in complex with cholix toxin to reveal important criteria for inhibitor binding and mechanism of action. These results provide new insight in antivirulence compound development for treating many bacterial diseases.
Newly Discovered and Characterized Antivirulence Compounds inhibit Bacterial Mono-ADP-ribosyltransferase Toxins.,Turgeon Z, Jorgensen R, Visschedyk D, Edwards PR, Legree S, McGregor C, Fieldhouse RJ, Mangroo D, Schapira M, Merrill AR Antimicrob Agents Chemother. 2010 Dec 6. PMID:21135177[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jorgensen R, Purdy AE, Fieldhouse RJ, Kimber MS, Bartlett DH, Rod Merrill A. Cholix toxin, a novel ADP-ribosylating factor from vibrio cholerae. J Biol Chem. 2008 Feb 25;. PMID:18276581 doi:M710008200
- ↑ Turgeon Z, White D, Jorgensen R, Visschedyk D, Fieldhouse RJ, Mangroo D, Merrill AR. Yeast as a tool for characterizing mono-ADP-ribosyltransferase toxins. FEMS Microbiol Lett. 2009 Nov;300(1):97-106. Epub 2009 Aug 31. PMID:19793133 doi:10.1111/j.1574-6968.2009.01777.x
- ↑ Turgeon Z, Jorgensen R, Visschedyk D, Edwards PR, Legree S, McGregor C, Fieldhouse RJ, Mangroo D, Schapira M, Merrill AR. Newly Discovered and Characterized Antivirulence Compounds inhibit Bacterial Mono-ADP-ribosyltransferase Toxins. Antimicrob Agents Chemother. 2010 Dec 6. PMID:21135177 doi:10.1128/AAC.01164-10
|
