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| - | [[Image:1chl.gif|left|200px]]<br /><applet load="1chl" size="450" color="white" frame="true" align="right" spinBox="true" | |
| - | caption="1chl" /> | |
| - | '''NMR SEQUENTIAL ASSIGNMENTS AND SOLUTION STRUCTURE OF CHLOROTOXIN, A SMALL SCORPION TOXIN THAT BLOCKS CHLORIDE CHANNELS'''<br /> | |
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| - | ==Overview== | + | ==NMR SEQUENTIAL ASSIGNMENTS AND SOLUTION STRUCTURE OF CHLOROTOXIN, A SMALL SCORPION TOXIN THAT BLOCKS CHLORIDE CHANNELS== |
| - | The solution structure of chlorotoxin, a small toxin purified from the, venom of the Leiurus quinquestriatus scorpion, has been determined using, 2D 1H NMR spectroscopy. Analysis of the NMR data shows that the structure, consists of a small three-stranded antiparallel beta-sheet packed against, an alpha-helix, thereby adopting the same fold as charybdotoxin and other, members of the short scorpion toxin family [Arseniev et al. (1984) FEBS, Lett. 165, 57-62; Martins et al. (1990) FEBS Lett. 260, 249-253; Bontems, et al. (1991) Science 254, 1521-1523]. Three disulfide bonds of, chlorotoxin (Cys5-Cys28, Cys16-Cys33, and Cys20-Cys35), cross-linking the, alpha-helix to the beta-sheet, follow the common pattern found in the, other short scorpion toxins. The fourth disulfide bridge (Cys2-Cys19), links the small N-terminal beta strand to the rest of the molecule, in, contrast to charybdotoxin where this disulfide bridge is absent and the, first strand interacts with the rest of the molecule by several contacts, between hydrophobic residues. Another structural difference between, chlorotoxin and charybdotoxin is observed at the level of the alpha-beta, turn. This difference is accompanied by a change in the electrostatic, potential surface, which is largely positive at the level of this turn in, chlorotoxin, whereas no such positive potential surface can be found at, the same position in charybdotoxin. In the latter protein, the positive, surface is formed by different charged residues situated on the, solvent-exposed site of the C-terminal beta-sheet.(ABSTRACT TRUNCATED AT, 250 WORDS) | + | <StructureSection load='1chl' size='340' side='right'caption='[[1chl]]' scene=''> |
| | + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[1chl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Leiurus_quinquestriatus Leiurus quinquestriatus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1CHL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1CHL FirstGlance]. <br> |
| | + | </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=1chl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1chl OCA], [https://pdbe.org/1chl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1chl RCSB], [https://www.ebi.ac.uk/pdbsum/1chl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1chl ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/CTXL_LEIQU CTXL_LEIQU] This toxin binds to the surface of glioma cells, and inhibits their proliferation without having effects on normal brain cells. In this context, this toxin has been described as a chloride channel inhibitor (probably ClC-3/CLCN3) by causing its internalization via caveolae (PubMed:16520829). It has also been described to selectively interact with MMP2 (in complex with MT1-MMP (MMP14) and TIMP2), to inhibit its enzymatic activity and to decrease its presence at the cell surface (PubMed:12454020).<ref>PMID:12454020</ref> <ref>PMID:16520829</ref> <ref>PMID:8383429</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The solution structure of chlorotoxin, a small toxin purified from the venom of the Leiurus quinquestriatus scorpion, has been determined using 2D 1H NMR spectroscopy. Analysis of the NMR data shows that the structure consists of a small three-stranded antiparallel beta-sheet packed against an alpha-helix, thereby adopting the same fold as charybdotoxin and other members of the short scorpion toxin family [Arseniev et al. (1984) FEBS Lett. 165, 57-62; Martins et al. (1990) FEBS Lett. 260, 249-253; Bontems et al. (1991) Science 254, 1521-1523]. Three disulfide bonds of chlorotoxin (Cys5-Cys28, Cys16-Cys33, and Cys20-Cys35), cross-linking the alpha-helix to the beta-sheet, follow the common pattern found in the other short scorpion toxins. The fourth disulfide bridge (Cys2-Cys19) links the small N-terminal beta strand to the rest of the molecule, in contrast to charybdotoxin where this disulfide bridge is absent and the first strand interacts with the rest of the molecule by several contacts between hydrophobic residues. Another structural difference between chlorotoxin and charybdotoxin is observed at the level of the alpha-beta turn. This difference is accompanied by a change in the electrostatic potential surface, which is largely positive at the level of this turn in chlorotoxin, whereas no such positive potential surface can be found at the same position in charybdotoxin. In the latter protein, the positive surface is formed by different charged residues situated on the solvent-exposed site of the C-terminal beta-sheet.(ABSTRACT TRUNCATED AT 250 WORDS) |
| | | | |
| - | ==About this Structure==
| + | NMR sequential assignments and solution structure of chlorotoxin, a small scorpion toxin that blocks chloride channels.,Lippens G, Najib J, Wodak SJ, Tartar A Biochemistry. 1995 Jan 10;34(1):13-21. PMID:7819188<ref>PMID:7819188</ref> |
| - | 1CHL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Leiurus_quinquestriatus Leiurus quinquestriatus]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1CHL OCA].
| + | |
| | | | |
| - | ==Reference==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | NMR sequential assignments and solution structure of chlorotoxin, a small scorpion toxin that blocks chloride channels., Lippens G, Najib J, Wodak SJ, Tartar A, Biochemistry. 1995 Jan 10;34(1):13-21. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=7819188 7819188]
| + | </div> |
| | + | <div class="pdbe-citations 1chl" style="background-color:#fffaf0;"></div> |
| | + | == References == |
| | + | <references/> |
| | + | __TOC__ |
| | + | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Leiurus quinquestriatus]] | | [[Category: Leiurus quinquestriatus]] |
| - | [[Category: Single protein]]
| + | [[Category: Lippens G]] |
| - | [[Category: Lippens, G.]] | + | [[Category: Najib J]] |
| - | [[Category: Najib, J.]] | + | [[Category: Tartar A]] |
| - | [[Category: Tartar, A.]] | + | [[Category: Wodak SJ]] |
| - | [[Category: Wodak, S.J.]] | + | |
| - | [[Category: neurotoxin]]
| + | |
| - | | + | |
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 12:27:44 2007''
| + | |
| Structural highlights
Function
CTXL_LEIQU This toxin binds to the surface of glioma cells, and inhibits their proliferation without having effects on normal brain cells. In this context, this toxin has been described as a chloride channel inhibitor (probably ClC-3/CLCN3) by causing its internalization via caveolae (PubMed:16520829). It has also been described to selectively interact with MMP2 (in complex with MT1-MMP (MMP14) and TIMP2), to inhibit its enzymatic activity and to decrease its presence at the cell surface (PubMed:12454020).[1] [2] [3]
Publication Abstract from PubMed
The solution structure of chlorotoxin, a small toxin purified from the venom of the Leiurus quinquestriatus scorpion, has been determined using 2D 1H NMR spectroscopy. Analysis of the NMR data shows that the structure consists of a small three-stranded antiparallel beta-sheet packed against an alpha-helix, thereby adopting the same fold as charybdotoxin and other members of the short scorpion toxin family [Arseniev et al. (1984) FEBS Lett. 165, 57-62; Martins et al. (1990) FEBS Lett. 260, 249-253; Bontems et al. (1991) Science 254, 1521-1523]. Three disulfide bonds of chlorotoxin (Cys5-Cys28, Cys16-Cys33, and Cys20-Cys35), cross-linking the alpha-helix to the beta-sheet, follow the common pattern found in the other short scorpion toxins. The fourth disulfide bridge (Cys2-Cys19) links the small N-terminal beta strand to the rest of the molecule, in contrast to charybdotoxin where this disulfide bridge is absent and the first strand interacts with the rest of the molecule by several contacts between hydrophobic residues. Another structural difference between chlorotoxin and charybdotoxin is observed at the level of the alpha-beta turn. This difference is accompanied by a change in the electrostatic potential surface, which is largely positive at the level of this turn in chlorotoxin, whereas no such positive potential surface can be found at the same position in charybdotoxin. In the latter protein, the positive surface is formed by different charged residues situated on the solvent-exposed site of the C-terminal beta-sheet.(ABSTRACT TRUNCATED AT 250 WORDS)
NMR sequential assignments and solution structure of chlorotoxin, a small scorpion toxin that blocks chloride channels.,Lippens G, Najib J, Wodak SJ, Tartar A Biochemistry. 1995 Jan 10;34(1):13-21. PMID:7819188[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Deshane J, Garner CC, Sontheimer H. Chlorotoxin inhibits glioma cell invasion via matrix metalloproteinase-2. J Biol Chem. 2003 Feb 7;278(6):4135-44. Epub 2002 Nov 25. PMID:12454020 doi:http://dx.doi.org/10.1074/jbc.M205662200
- ↑ McFerrin MB, Sontheimer H. A role for ion channels in glioma cell invasion. Neuron Glia Biol. 2006 Feb;2(1):39-49. PMID:16520829 doi:http://dx.doi.org/10.1017/S17440925X06000044
- ↑ DeBin JA, Maggio JE, Strichartz GR. Purification and characterization of chlorotoxin, a chloride channel ligand from the venom of the scorpion. Am J Physiol. 1993 Feb;264(2 Pt 1):C361-9. PMID:8383429
- ↑ Lippens G, Najib J, Wodak SJ, Tartar A. NMR sequential assignments and solution structure of chlorotoxin, a small scorpion toxin that blocks chloride channels. Biochemistry. 1995 Jan 10;34(1):13-21. PMID:7819188
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