2knn: Difference between revisions
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< | ==Solution structure of the cyclotide cycloviolacin O2 with Glu6 methylated (cyO2Me)== | ||
<StructureSection load='2knn' size='340' side='right'caption='[[2knn]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | |||
You may | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2knn]] 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=2KNN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KNN FirstGlance]. <br> | |||
</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=GME:5-O-METHYL-GLUTAMIC+ACID'>GME</scene></td></tr> | |||
-- | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2knm|2knm]]</div></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=2knn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2knn OCA], [https://pdbe.org/2knn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2knn RCSB], [https://www.ebi.ac.uk/pdbsum/2knn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2knn ProSAT]</span></td></tr> | |||
</table> | |||
== 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> | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kn/2knn_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=2knn ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:19735083</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2knn" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
< | |||
[[Category: Viola odorata]] | [[Category: Viola odorata]] | ||
[[Category: Rosengren, K | [[Category: Rosengren, K]] | ||
[[Category: Circular protein]] | [[Category: Circular protein]] | ||
[[Category: Cyclic cystine knot]] | [[Category: Cyclic cystine knot]] | ||
| Line 36: | Line 46: | ||
[[Category: Plant defense]] | [[Category: Plant defense]] | ||
[[Category: Plant protein]] | [[Category: Plant protein]] | ||
Latest revision as of 10:34, 2 February 2022
Solution structure of the cyclotide cycloviolacin O2 with Glu6 methylated (cyO2Me)Solution structure of the cyclotide cycloviolacin O2 with Glu6 methylated (cyO2Me)
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 PubMedCyclotides 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
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