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| | ==Solution structure of cycloviolacin O2== | | ==Solution structure of cycloviolacin O2== |
| - | <StructureSection load='2kcg' size='340' side='right'caption='[[2kcg]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2kcg' size='340' side='right'caption='[[2kcg]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[2kcg]] 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=2KCG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KCG FirstGlance]. <br> | | <table><tr><td colspan='2'>[[2kcg]] 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=2KCG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KCG FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2kch|2kch]]</div></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'>[https://proteopedia.org/fgij/fg.htm?mol=2kcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kcg OCA], [https://pdbe.org/2kcg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kcg RCSB], [https://www.ebi.ac.uk/pdbsum/2kcg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kcg 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=2kcg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kcg OCA], [https://pdbe.org/2kcg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kcg RCSB], [https://www.ebi.ac.uk/pdbsum/2kcg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kcg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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/kc/2kcg_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kc/2kcg_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: Wang, C K]] | + | [[Category: Wang CK]] |
| - | [[Category: Cyclic cystine knot]]
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| - | [[Category: Cytolysis]]
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| - | [[Category: Hemolysis]]
| + | |
| - | [[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 cyclic proteins produced by plants for defense against pests. Because of their remarkable stability and diverse bioactivities, they have a range of potential therapeutic applications. The bioactivities of cyclotides are believed to be mediated through membrane interactions. To determine the structural basis for the biological activity of the two major subfamilies of cyclotides, we determined the conformation and orientation of kalata B2 (kB2), a Mobius cyclotide, and cycloviolacin O2 (cO2), a bracelet cyclotide, bound to dodecylphosphocholine micelles, using NMR spectroscopy in the presence and absence of 5- and 16-doxylstearate relaxation probes. Analysis of binding curves using the Langmuir isotherm indicated that cO2 and kB2 have association constants of 7.0 x 10(3) M(-1) and 6.0 x 10(3) M(-1), respectively, consistent with the notion that they are bound near the surface, rather than buried deeply within the micelle. This suggestion is supported by the selective broadening of micelle-bound cyclotide NMR signals upon addition of paramagnetic Mn ions. The cyclotides from the different subfamilies exhibited clearly different binding orientations at the micelle surface. Structural analysis of cO2 confirmed that the main element of the secondary structure is a beta-hairpin centered in loop 5. A small helical turn is present in loop 3. Analysis of the surface profile of cO2 shows that a hydrophobic patch stretches over loops 2 and 3, in contrast to the hydrophobic patch of kB2, which predominantly involves loops 2 and 5. The different location of the hydrophobic patches in the two cyclotides explains their different binding orientations and provides an insight into the biological activities of cyclotides.
Despite a conserved cystine knot motif, different cyclotides have different membrane binding modes.,Wang CK, Colgrave ML, Ireland DC, Kaas Q, Craik DJ Biophys J. 2009 Sep 2;97(5):1471-81. PMID:19720036[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
- ↑ Wang CK, Colgrave ML, Ireland DC, Kaas Q, Craik DJ. Despite a conserved cystine knot motif, different cyclotides have different membrane binding modes. Biophys J. 2009 Sep 2;97(5):1471-81. PMID:19720036 doi:10.1016/j.bpj.2009.06.032
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