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| ==Solution Structure of kalata B1[W23WW]== | | ==Solution Structure of kalata B1[W23WW]== |
- | <StructureSection load='2mn1' size='340' side='right' caption='[[2mn1]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mn1' size='340' side='right'caption='[[2mn1]]' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[2mn1]] is a 1 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MN1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MN1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mn1]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Oldenlandia_affinis Oldenlandia affinis]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MN1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MN1 FirstGlance]. <br> |
- | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2mn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mn1 OCA], [http://pdbe.org/2mn1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mn1 RCSB], [http://www.ebi.ac.uk/pdbsum/2mn1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mn1 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 20 models</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=2mn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mn1 OCA], [https://pdbe.org/2mn1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mn1 RCSB], [https://www.ebi.ac.uk/pdbsum/2mn1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mn1 ProSAT]</span></td></tr> |
| </table> | | </table> |
| + | == Function == |
| + | [https://www.uniprot.org/uniprot/KAB1_OLDAF KAB1_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.<ref>PMID:17534989</ref> <ref>PMID:12779323</ref> |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Chaousis, S]] | + | [[Category: Large Structures]] |
- | [[Category: Craik, D J]] | + | [[Category: Oldenlandia affinis]] |
- | [[Category: Henriques, S T]] | + | [[Category: Chaousis S]] |
- | [[Category: Huang, Y H]] | + | [[Category: Craik DJ]] |
- | [[Category: Wang, C K]] | + | [[Category: Henriques ST]] |
- | [[Category: Cyclotide]] | + | [[Category: Huang YH]] |
- | [[Category: Unknown function]] | + | [[Category: Wang CK]] |
| Structural highlights
Function
KAB1_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 PubMed
Cyclotides, 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
- ↑ Plan MR, Goransson U, Clark RJ, Daly NL, Colgrave ML, Craik DJ. The cyclotide fingerprint in oldenlandia affinis: elucidation of chemically modified, linear and novel macrocyclic peptides. Chembiochem. 2007 Jun 18;8(9):1001-11. PMID:17534989 doi:http://dx.doi.org/10.1002/cbic.200700097
- ↑ Barry DG, Daly NL, Clark RJ, Sando L, Craik DJ. Linearization of a naturally occurring circular protein maintains structure but eliminates hemolytic activity. Biochemistry. 2003 Jun 10;42(22):6688-95. PMID:12779323 doi:http://dx.doi.org/10.1021/bi027323n
- ↑ Troeira Henriques S, Huang YH, Chaousis S, Wang CK, Craik DJ. Anticancer and toxic properties of cyclotides are dependent on phosphatidylethanolamine phospholipid targeting. Chembiochem. 2014 Sep 5;15(13):1956-65. doi: 10.1002/cbic.201402144. Epub 2014, Aug 5. PMID:25099014 doi:http://dx.doi.org/10.1002/cbic.201402144
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