kalata S(37) Protein Card

General Information
Name kalata S
Alternative name(s) varv peptide A
Class Cyclotide
Technique MS,NGS
Average Mass 2878.25
Monoisotopic Mass 2876.13
m/z M+H 2878.25
ProteinType Wild type
Organism Viola odorata
Oldenlandia affinis
Viola tricolor
Viola arvensis
Viola baoshanensis
Viola yedoensis
Viola biflora
Viola philippica
Viola ignobilis
Viola uliginosa
Viola sumatrana Miq
Viola arcuata
Palicourea sessilis
Viola betonicifolia
Viola anagae
Notes Also described in GenBank with the id 17433131 and in UnirotKB/SwissProt with id P58446 and P85525. Can be extracted from plant material by microwave-assisted extraction, less efficient than maceration. (Farhadpour et al., 2016). Kalata S was also found in the petiole tissue Viola odorata by Aslam et al. (2022) using UPLC-Q-TOF/MS and LC-MS/MS analysis.
Cyclic Yes

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
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
Vitri A, varv A and varv E shown to possess cytotoxic activity in cancer cells. [...]Svangard E et al. (2004) J Nat Prod 67:144-7
Cycloviolacins Y4 and Y5 are the most hemolytic of the new cyclotides, both being more potent than the prototypic cyclotide kalata B1. By contrast, cycloviolacin Y1 is substantially less active than all of the other cyclotides tested. [...]Wang CK et al. (2007) J Nat Prod 71:47-52
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
All cyclotides tested from V. yedoensis demonstrated anti-HIV activity, with cycloviolacin Y5 being the most potent. [...]Wang CK et al. (2007) J Nat Prod 71:47-52
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
Chemical Shift
[...]Niyomploy et al. (2016) Peptide Science 106:796-805

Svangard E, Goransson U, Hocaoglu Z, Gullbo J, Larsson R, Claeson P, Bohlin L (2004) Cytotoxic cyclotides from Viola tricolor. J Nat Prod 67:144-7
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
Goransson U, Luijendijk T, Johansson S, Bohlin L, Claeson P (1999) Seven novel macrocyclic polypeptides from Viola arvensis. J Nat Prod 62:283-6
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
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
Wang CK, Colgrave ML, Gustafson KR, Ireland DC, Göransson U, Craik DJ (2007) Anti-HIV Cyclotides from the CHinese Medicinal Herb Viola yedoensis J Nat Prod 71:47-52
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
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
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
Hashempour,H., Ghassempour,A., Daly,N.L., Spengler,B. and Römpp,A. (2011) Analysis of cyclotides in Viola ignobilis by Nano liquid chromatography fourier transform mass spectrometry. Protein Pept. Lett. 18:747-752
Farhadpour,M., Hashempour,H., Talebpour,Z., A-Bagheri,N., Shushtarian,M.S., Gruber,C.W. and Ghassempour,A. (2016) Microwave-assisted extraction of cyclotides from Viola ignobilis. Anal. Biochem. 497:83-89
Slazak, B., Jacobsson, E., Kuta, E. and Göransson, U. (2015) Exogenous plant hormones and cyclotide expression in Viola uliginosa (Violaceae Phytochemistry 117:527-536
Niyomploy, P., Chan, L.Y., Poth, A.G., Colgrave, M.L., Sangvanich, P. and Craik, D.J. (2016) Discovery, isolation, and structural characterization of cyclotides from Viola sumatrana Miq Peptide Science 106:796-805
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
Pinto,M.E.F., Chan,L.Y., Koehbach,J., Devi,S., Gründemann,C., Gruber,C.W., Gomes,M., Bolzani,V.S., Cilli,E.M., and Craik,D.J. (2021) Cyclotides from Brazilian Palicourea sessilis and Their Effects on Human Lymphocytes. J Nat Prod 84:81-90
Aslam,L., Kaur,R., Sharma,V., Kapoor,N. and Mahajan,R. (2021) Isolation and characterization of cyclotides from the leaves of Viola odorata L. using peptidomic and bioinformatic approach. 3 Biotech 11:211-0
Rajendran,S., Slazak,B., Mohotti,S., Strömstedt,A.A., Göransson,U. and Gunasekera,S. (2021) Tropical vibes from Sri Lanka - cyclotides from Viola betonicifolia by transcriptome and mass spectrometry analysis. Phytochemistry 187:112749-0
Slazak,B., Kaltenböck,K., Steffen,K., Rogala,M., Rodríguez-Rodríguez,P., Nilsson,A., Shariatgorji,R. and Göransson,U. (2021) Cyclotide host-defense tailored for species and environments in violets from the Canary Islands. Sci Rep 11:12452-0
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
Aslam,L., Kaur,R., Hussain,S., Kapoor,N., and Mahajan,R. (2022) LC-MS/MS identification and structural characterization of isolated cyclotides from precursor sequences of Viola odorata L. petiole tissue using computational approach. J Biosci 47:50-0

Protein precursor(s) cyclotide k1 precursor
cyclotide precursor 7c
cyclotide precursor 6b
Viba17 precursor
cyclotide k1 precursor
vocC precursor (partial)
kalata S precursor [partial]
vian 1 precursor [partial]
Nucleic acids cyclotide k1 precursor
cyclotide precursor 6b mRNA
cyclotide precursor 6c mRNA
cyclotide precursor 7c mRNA
Links GenBank P58446.1
SwissProt P58458

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