2mn1
From Proteopedia
Solution Structure of kalata B1[W23WW]
Structural highlights
FunctionKAB1_OLDAF Probably participates in a plant defense mechanism. Has antibiotic activity. Has a diuretic effect. Has a uterotonic effect in humans. Active against the Gram-positive S.aureus with a minimum inhibition concentration of approximately 0.2 microM. Relatively ineffective against Gram-negative bacteria such as E.coli and P.aeruginosa. Inhibitory effect on the growth and development of larvae from H.punctigera. The unmodified form has hemolytic activity, the oxidized form lacks hemolytic activity. If the protein is linearized, hemolytic activity is lost.[1] [2] Publication Abstract from PubMedCyclotides, ultrastable disulfide-rich cyclic peptides, can be engineered to bind and inhibit specific cancer targets. In addition, some cyclotides are toxic to cancer cells, though not much is known about their mechanisms of action. Here we delineated the potential mode of action of cyclotides towards cancer cells. A novel set of analogues of kalata B1 (the prototypic cyclotide) and kalata B2 and cycloviolacin O2 were examined for their membrane-binding affinity and selectivity towards cancer cells. By using solution-state NMR, surface plasmon resonance, flow cytometry and bioassays we show that cyclotides are toxic against cancer and non-cancerous cells and their toxicity correlates with their ability to target and disrupt lipid bilayers that contain phosphatidylethanolamine phospholipids. Our results suggest that the potential of cyclotides as anticancer therapeutics might best be realised by combining their amenability to epitope engineering with their ability to bind cancer cell membranes. Anticancer and toxic properties of cyclotides are dependent on phosphatidylethanolamine phospholipid targeting.,Troeira Henriques S, Huang YH, Chaousis S, Wang CK, Craik DJ Chembiochem. 2014 Sep 5;15(13):1956-65. doi: 10.1002/cbic.201402144. Epub 2014, Aug 5. PMID:25099014[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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