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| | ==Solution structure of the cyclotide cycloviolacin O2== | | ==Solution structure of the cyclotide cycloviolacin O2== |
| - | <StructureSection load='2knm' size='340' side='right'caption='[[2knm]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2knm' size='340' side='right'caption='[[2knm]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2knm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Viola_odorata Viola odorata]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KNM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=2KNM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2knm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Viola_odorata Viola odorata]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KNM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KNM FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2knn|2knn]]</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=2knm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2knm OCA], [http://pdbe.org/2knm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2knm RCSB], [http://www.ebi.ac.uk/pdbsum/2knm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2knm 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=2knm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2knm OCA], [https://pdbe.org/2knm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2knm RCSB], [https://www.ebi.ac.uk/pdbsum/2knm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2knm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CYO2_VIOOD CYO2_VIOOD]] Probably participates in a plant defense mechanism. Has strong cytotoxic activity against a variety of drug-resistant and drug-sensitive human tumor cell lines, and against primary chronic lymphocytic leukemia and ovarian carcinoma cells. Has weaker cytotoxic activity against normal lymphocytes. Has hemolytic activity.<ref>PMID:16872274</ref> <ref>PMID:12477048</ref> | + | [https://www.uniprot.org/uniprot/CYO2_VIOOD CYO2_VIOOD] Probably participates in a plant defense mechanism. Has strong cytotoxic activity against a variety of drug-resistant and drug-sensitive human tumor cell lines, and against primary chronic lymphocytic leukemia and ovarian carcinoma cells. Has weaker cytotoxic activity against normal lymphocytes. Has hemolytic activity.<ref>PMID:16872274</ref> <ref>PMID:12477048</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kn/2knm_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kn/2knm_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Viola odorata]] | | [[Category: Viola odorata]] |
| - | [[Category: Rosengren, K]] | + | [[Category: Rosengren K]] |
| - | [[Category: Circular protein]]
| + | |
| - | [[Category: Cyclic cystine knot]]
| + | |
| - | [[Category: Cyclotide]]
| + | |
| - | [[Category: Cytolysis]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Hemolysis]]
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| - | [[Category: Knottin]]
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| - | [[Category: Plant defense]]
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| - | [[Category: Plant protein]]
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| Structural highlights
Function
CYO2_VIOOD Probably participates in a plant defense mechanism. Has strong cytotoxic activity against a variety of drug-resistant and drug-sensitive human tumor cell lines, and against primary chronic lymphocytic leukemia and ovarian carcinoma cells. Has weaker cytotoxic activity against normal lymphocytes. Has hemolytic activity.[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Cyclotides are a large family of plant peptides that are characterised by a head-to-tail circular backbone and three disulfide bonds that are arranged in a cystine knot. This unique structural feature, which is referred to as a cyclic cystine knot, gives the cyclotides remarkable stability against chemical and biological degradation. In addition to their natural function as insecticides for plant defence, the cyclotides have a range of bioactivities with pharmaceutical relevance, including cytotoxicity against cancer cell lines. A glutamic acid residue, aside from the invariable disulfide array, is the most conserved feature throughout the cyclotide family, and it has recently been shown to be crucial for biological activity. Here we have used solution-state NMR spectroscopy to determine the three-dimensional structures of the potent cytotoxic cyclotide cycloviolacin O2, and an inactive analogue in which this conserved glutamic acid has been methylated. The structures of the peptides show that the glutamic acid has a key structural role in coordinating a set of hydrogen bonds in native cycloviolacin O2; this interaction is disrupted in the methylated analogue. The proposed mechanism of action of cyclotides is membrane disruption and these results suggest that the glutamic acid is linked to cyclotide function by stabilising the structure to allow efficient aggregation in membranes, rather than in a direct interaction with a target receptor.
The conserved glu in the cyclotide cycloviolacin O2 has a key structural role.,Goransson U, Herrmann A, Burman R, Haugaard-Jonsson LM, Rosengren KJ Chembiochem. 2009 Sep 21;10(14):2354-60. PMID:19735083[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Ireland DC, Colgrave ML, Craik DJ. A novel suite of cyclotides from Viola odorata: sequence variation and the implications for structure, function and stability. Biochem J. 2006 Nov 15;400(1):1-12. PMID:16872274 doi:BJ20060627
- ↑ Lindholm P, Goransson U, Johansson S, Claeson P, Gullbo J, Larsson R, Bohlin L, Backlund A. Cyclotides: a novel type of cytotoxic agents. Mol Cancer Ther. 2002 Apr;1(6):365-9. PMID:12477048
- ↑ Goransson U, Herrmann A, Burman R, Haugaard-Jonsson LM, Rosengren KJ. The conserved glu in the cyclotide cycloviolacin O2 has a key structural role. Chembiochem. 2009 Sep 21;10(14):2354-60. PMID:19735083 doi:10.1002/cbic.200900342
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