1dw5: Difference between revisions
New page: left|200px<br /><applet load="1dw5" size="450" color="white" frame="true" align="right" spinBox="true" caption="1dw5" /> '''NMR STRUCTURE OF OMEGA-CONOTOXIN MVIIA: NO C... |
No edit summary |
||
| (15 intermediate revisions by the same user not shown) | |||
| Line 1: | Line 1: | ||
== | ==NMR STRUCTURE OF OMEGA-CONOTOXIN MVIIA: NO CONSTRAINTS ON DISULPHIDE BRIDGES== | ||
omega-Conotoxin MVIIA is a 25-residue, disulfide-bridged polypeptide from | <StructureSection load='1dw5' size='340' side='right'caption='[[1dw5]]' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[1dw5]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_magus Conus magus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DW5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1DW5 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR, 25 models</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></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=1dw5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dw5 OCA], [https://pdbe.org/1dw5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1dw5 RCSB], [https://www.ebi.ac.uk/pdbsum/1dw5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1dw5 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/O17A_CONMA O17A_CONMA] Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels. This toxin blocks Cav2.2/CACNA1B calcium channels (IC(50)=0.67-208 nM) (PubMed:26344359, PubMed:34589389, PubMed:7826361). It acts by neutralizing the outer electronegativity and sterically hindering the ion access path to the entrance of the channel selectivity filter (PubMed:34234349). It also shows antiproliferative effects on different glioma cell lines (M059J, U-138MG and U-251MG) (PubMed:28202361). In vivo, is lethal to fish (PubMed:26344359, PubMed:34589389). In vivo, injection into mammals induces adverse effects, such as tremor, diminution of spontaneous locomotor activity and bad coordinated locomotion (PubMed:26344359). In addition, it causes reduction of tumor area in the mouse glioma model, that is induced by the orthotopic injection of GL261 cells into the brain (PubMed:28202361).<ref>PMID:26344359</ref> <ref>PMID:34234349</ref> <ref>PMID:7826361</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
omega-Conotoxin MVIIA is a 25-residue, disulfide-bridged polypeptide from the venom of the sea snail Conus magus that binds to neuronal N-type calcium channels. It forms a compact folded structure, presenting a loop between Cys8 and Cys15 that contains a set of residues critical for its binding. The loop does not have a unique defined structure, nor is it intrinsically flexible. Broadening of a subset of resonances in the NMR spectrum at low temperature, anomalous temperature dependence of the chemical shifts of some resonances, and exchange contributions to J(0) from (13)C relaxation measurements reveal that conformational exchange affects the residues in this loop. The effects of this exchange on the calculated structure of omega-conotoxin MVIIA are discussed. The exchange appears to be associated with a change in the conformation of the disulfide bridge Cys8-Cys20. The implications for the use of the omega-conotoxins as a scaffold for carrying other functions is discussed. | |||
Structural and dynamic characterization of omega-conotoxin MVIIA: the binding loop exhibits slow conformational exchange.,Atkinson RA, Kieffer B, Dejaegere A, Sirockin F, Lefevre JF Biochemistry. 2000 Apr 11;39(14):3908-19. PMID:10747778<ref>PMID:10747778</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
[[Category: | <div class="pdbe-citations 1dw5" style="background-color:#fffaf0;"></div> | ||
[[Category: Atkinson | == References == | ||
[[Category: Dejaegere | <references/> | ||
[[Category: Kieffer | __TOC__ | ||
[[Category: Lefevre | </StructureSection> | ||
[[Category: Sirockin | [[Category: Conus magus]] | ||
[[Category: Large Structures]] | |||
[[Category: Atkinson RA]] | |||
[[Category: Dejaegere A]] | |||
[[Category: Kieffer B]] | |||
[[Category: Lefevre J-F]] | |||
[[Category: Sirockin F]] | |||
Latest revision as of 02:54, 21 November 2024
NMR STRUCTURE OF OMEGA-CONOTOXIN MVIIA: NO CONSTRAINTS ON DISULPHIDE BRIDGESNMR STRUCTURE OF OMEGA-CONOTOXIN MVIIA: NO CONSTRAINTS ON DISULPHIDE BRIDGES
Structural highlights
FunctionO17A_CONMA Omega-conotoxins act at presynaptic membranes, they bind and block voltage-gated calcium channels. This toxin blocks Cav2.2/CACNA1B calcium channels (IC(50)=0.67-208 nM) (PubMed:26344359, PubMed:34589389, PubMed:7826361). It acts by neutralizing the outer electronegativity and sterically hindering the ion access path to the entrance of the channel selectivity filter (PubMed:34234349). It also shows antiproliferative effects on different glioma cell lines (M059J, U-138MG and U-251MG) (PubMed:28202361). In vivo, is lethal to fish (PubMed:26344359, PubMed:34589389). In vivo, injection into mammals induces adverse effects, such as tremor, diminution of spontaneous locomotor activity and bad coordinated locomotion (PubMed:26344359). In addition, it causes reduction of tumor area in the mouse glioma model, that is induced by the orthotopic injection of GL261 cells into the brain (PubMed:28202361).[1] [2] [3] Publication Abstract from PubMedomega-Conotoxin MVIIA is a 25-residue, disulfide-bridged polypeptide from the venom of the sea snail Conus magus that binds to neuronal N-type calcium channels. It forms a compact folded structure, presenting a loop between Cys8 and Cys15 that contains a set of residues critical for its binding. The loop does not have a unique defined structure, nor is it intrinsically flexible. Broadening of a subset of resonances in the NMR spectrum at low temperature, anomalous temperature dependence of the chemical shifts of some resonances, and exchange contributions to J(0) from (13)C relaxation measurements reveal that conformational exchange affects the residues in this loop. The effects of this exchange on the calculated structure of omega-conotoxin MVIIA are discussed. The exchange appears to be associated with a change in the conformation of the disulfide bridge Cys8-Cys20. The implications for the use of the omega-conotoxins as a scaffold for carrying other functions is discussed. Structural and dynamic characterization of omega-conotoxin MVIIA: the binding loop exhibits slow conformational exchange.,Atkinson RA, Kieffer B, Dejaegere A, Sirockin F, Lefevre JF Biochemistry. 2000 Apr 11;39(14):3908-19. PMID:10747778[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||||||