cycloviolacin O13(170) Protein Card

General Information
Name cycloviolacin O13
Alternative name(s) cO13,CyO13
Class Cyclotide
Technique MS,Amino acid analysis
Average Mass 3124.69
Monoisotopic Mass 3122.37
m/z M+H 3124.69
ProteinType Wild type
Organism Viola odorata
Hybanthus enneaspermus
Viola baoshanensis
Viola uliginosa
Viola arcuata
Viola austrosinensis
Notes <i>H. enneaspermus</i>: fully sequenced by MS/MS fragment matching (ProteinPilot) but could not be isolated from the plant for individual MS/MS sequencing (Du et al., 2020).
Cyclic Yes

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
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
Cycloviolacin O13, O14 and O24 inhibited the cytopathic effects of HIV-1 infection in cultured human T-lymphoblast (CEM-SS) cells with antiviral cytoprotective concentrations (EC50) of 320, 440, and 308 nM, while the cytotoxic concentration (IC50) was 6.4, 4.8, and 6.2 uM, respectively [...]Ireland DC et al. (2008) Biopolymers 90:51-60
Enzymatic Digest
Cycloviolacin O13, O14, O16 and O24 were tested for their stability against proteolytic degradation by pepsin, trypsin and thermolysin.No degradation by proteases was observed for any of the cyclotides tested following 6 hours of incubation with enzymes, while the linear control peptide was completely degraded in less than 5 minutes. [...]Ireland DC et al. (2006) Biochem J. 400:1-12
CyO2,CyO3,CyO13,CyO19 have deterrent activity on M.persicae. [...]Dancewicz,K. et al. (2020) Journal of Insect Physiology 122:104025-0
Cancer Cell Toxicity
CyO2, CyO13, kalata B1, and varv peptide A exhibited dose-dependent cytotoxicity in MTT assays with IC50 values of 2.15-7.93 uM against human brain astrocytoma cells (U-87 MG) and human bone marrow derived neuroblastoma cells (SH-SY5Y). CyO2 and varv peptide A also sensitized SH-SY5Y and U-87 MG cells to temozolomide (TMZ) which is the only effective chemotherapeutic drug used to treat glioblastoma multiforme (GBM). [...]Gerlach,S.L. et al. (2022) J Nat Prod 85:34-46

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
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
Hellinger,R., Koehbach,J., Soltis,D.E., Carpenter,E.J., Wong,G.K. and Gruber,C.W. (2015) Peptidomics of Circular Cysteine-Rich Plant Peptides: Analysis of the Diversity of Cyclotides from Viola tricolor by Transcriptome and Proteome Mining. J. Proteome Res. 14:4851-4862
Slazak,B., Kapusta,M., Strömstedt,A.A., S?omka,A., Krychowiak,M., Shariatgorji,M., Andrén,P.E., Bohdanowicz,J., Kuta,E., and Göransson,U. (2018) How Does the Sweet Violet (Viola odorata L.) Fight Pathogens and Pests - Cyclotides as a Comprehensive Plant Host Defense System Frontiers in plant science 9:0-0
Zhang, J., Li, J., Huang, Z., Yang, B., Zhang, X., Li, D., Craik, D.J., Baker, A.J., Shu, W. and Liao, B. (2015) Transcriptomic screening for cyclotides and other cysteine-rich proteins in the metallophyte Viola baoshanensis. Journal of plant physiology 178:17-26
Slazak, B., Jacobsson, E., Kuta, E. and Göransson, U. (2015) Exogenous plant hormones and cyclotide expression in Viola uliginosa (Violaceae Phytochemistry 117:527-536
Dancewicz,K., Slazak,B., Kie?kiewicz,M., Kapusta,M., Bohdanowicz,J., and Gabry?,B. (2020) Behavioral and physiological effects of Viola spp. cyclotides on Myzus persicae (Sulz.) Journal of Insect Physiology 122:104025-0
Du,Q., Chan,L.Y., Gilding,E.K., Henriques,S.T., Condon,N.D., Ravipati,A.S., Kaas,Q., Huang,Y.H. and Craik,D.J. (2020) Discovery and mechanistic studies of cytotoxic cyclotides from the medicinal herb Hybanthus enneaspermus. J Biol Chem 295:10911-10925
Dang,T.T., Chan,L.Y., Huang,Y.H., Nguyen,L.T.T., Kaas,Q., Huynh,T. and Craik,D.J. (2020) Exploring the Sequence Diversity of Cyclotides from Vietnamese Viola Species. J Nat Prod 83:1817-1828
Gerlach,S.L., Dunlop,R.A., Metcalf,J.S., Banack,S.A., and Cox,P.A. (2022) Cyclotides Chemosensitize Glioblastoma Cells to Temozolomide. J Nat Prod 85:34-46

Protein precursor(s) cyclotide c3 precursor
Nucleic acids cyclotide c3 precursor
Links GenBank Q5USN8.1
SwissProt Q5USN8

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