cycloviolacin O2(21) Protein Card

General Information
Name cycloviolacin O2
Alternative name(s) cO2
Sequence GIPCGESCVWIPCISSAIGCSCKSKVCYRN
Class Cyclotide
Technique MS
Average Mass 3140.69
Monoisotopic Mass 3138.37
m/z M+H 3140.69
ProteinType Wild type
Parent
Organism Viola odorata
Viola biflora
Viola philippica
Notes
Cyclic Yes

Assay
Cancer Cell Toxicity
Psyle A, psyle C, psyle E and cycloviolacin O2 shown to possess cytotoxic activity in cancer cells. [...]Gerlach SL et al. (2010) Biopolymers 94:617-625
Studies using calcein assay and HeLa cells showed that at 10 uM, the increase in calcein leakage is very rapid. [...]Svangard E et al. (2007) J Nat Prod 70:643-647
Cell viability and morphology studies on the human lymphoma cell line U-937 GTB showed that cells exposed to cycloviolacin O2 displayed disintegrated cell membranes within 5 min. [...]Svangard E et al. (2007) J Nat Prod 70:643-647
All three cyclotides, varv A, varv F, and cycloviolacin O2, exhibited strong cytotoxic activities, which varied in a dose-dependent manner. [...]Lindholm P et al. (2002) Mol Cancer Ther 1:365-369
Glutamic acid mutant had reduced activity [...]Herrmann A et al. (2006) Cell Mol Life Sci 63:235-45
Nematocidal
Motility affected by cyclotides [...]Colgrave ML et al. (2008) Chembiochem 9:1939-1945
A range of natural variants were selected based on net charge and/or hydrophobicity and were tested alongside the prototypic cyclotide kB1 in larval development assays with H. contortus and T. colubriformis. [...]Colgrave ML et al. (2008) Chembiochem 9:1939-1945
Membrane Binding Assay
Tb3+/DPA Liposome Assay on cycloviolacin O2 showed an effect within minutes [...]Svangard E et al. (2007) J Nat Prod 70:643-647
Hemolytic
At a concentration of 25 ºM, a more than 6-fold difference exists between the most hemolyticcyclotide, cycloviolacin O24 (~75% hemolysis), and the least hemolytic cyclotide cycloviolacin O14 (~11% hemolysis). The sensitivity of hemolytic activity to variations in the peptide sequence is evident when comparing cycloviolacin O2 and O13. Here, the only sequence deviation is a single residue substitution of a serine in loop 3 of O2 (HD50 ~36 ºM) to an alanine in the homologous position in O13 (HD50 ~11 ºM). The loss of this single hydroxy group changes the HD50 more than three-fold. [...]Ireland DC et al. (2006) Biochem J. 400:1-12
Anti-barnacle
Anti-barnacle activity shown for cycloviolacin O2 [...]Goransson U et al. (2004) J Nat Prod 67:1287-90

References
Goransson U, Sjogren M, Svangard E, Claeson P, Bohlin L (2004) Reversible antifouling effect of the cyclotide cycloviolacin O2 against barnacles. J Nat Prod 67:1287-90
Dutton JL, Renda RF, Waine C, Clark RJ, Daly NL, Jennings CV, Anderson MA, Craik DJ (2004) Conserved structural and sequence elements implicated in the processing of gene-encoded circular proteins. J Biol Chem 279:46858-67
Trabi M, Craik DJ (2004) Tissue-specific expression of head-to-tail cyclized miniproteins in Violaceae and structure determination of the root cyclotide Viola hederacea root cyclotide1. Plant Cell 16:2204-16
Craik DJ, Daly NL, Bond T, Waine C (1999) Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif. J Mol Biol 294:1327-36
Ireland DC, Colgrave ML, Craik DJ (2006) A novel suite of cyclotides from Viola odorata: sequence variation and the implications for structure, function and stability. Biochem J. 400:1-12
Herrmann A, Svangard E, Claeson P, Gullbo J, Bohlin L, Goransson U (2006) Key role of glutamic acid for the cytotoxic activity of the cyclotide cycloviolacin O2. Cell Mol Life Sci 63:235-45
Lindholm P, Goransson U, Johansson S, Claeson P, Gullbo J, Larsson R, Bohlin L, Backlund A (2002) Cyclotides: a novel type of cytotoxic agents. Mol Cancer Ther 1:365-369
Svangard E, Burman R, Gunasekera S, Lovborg H, Gullbo J, Goransson U (2007) Mechanism of action of cytotoxic cyclotides: cycloviolacin O2 disrupts lipid membranes. J Nat Prod 70:643-647
Herrmann A, Burman R, Mylne JS, Karlsson G, Gullbo J, Craik DJ, Clark RJ, Goransson U (2008) The alpine violet, Viola biflora, is a rich source of cyclotides with potent cytotoxicity Phytochemistry 69:939-952
Tang J, Wang CK, Pan X, Yan H, Zeng G, Xu W, He W, Daly NL, Craik DJ, Tan N (2010) Isolation and characterization of cytotoxic cyclotides from Viola tricolor. Peptides 31:1434-1440
Gerlach SL, Rathinakumar R, Chakravarty G, Göransson U, Wimley WC, Darwin SP, Mondal D (2010) Anticancer and chemosensitizing abilities of cycloviolacin 02 from Viola odorata and psyle cyclotides from Psychotria leptothyrsa. Biopolymers 94:617-625
He,W., Chan,L.Y., Zeng,G., Daly,N.L., Craik,D.J. and Tan,N. (2011) Isolation and characterization of cytotoxic cyclotides from Viola philippica. Peptides 32:1719-1723
Burman,R., Strömstedt,A.A., Malmsten,M. and Göransson,U. (2011) Cyclotide-membrane interactions: defining factors of membrane binding, depletion and disruption. Biochim. Biophys. Acta 1808:2665-2673

Cross-references
Nucleic acids cyclotide c3 precursor
Structure Solution structure of cycloviolacin O2.
Solution structure of the cyclotide cycloviolacin O2
Links SwissProt P58434

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