View source for 1rmk


==Solution structure of conotoxin MrVIB==
<StructureSection load='1rmk' size='340' side='right'caption='[[1rmk]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1rmk]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Conus_marmoreus Conus marmoreus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1RMK OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1RMK FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1rmk FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1rmk OCA], [https://pdbe.org/1rmk PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1rmk RCSB], [https://www.ebi.ac.uk/pdbsum/1rmk PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1rmk ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/O16B_CONMR O16B_CONMR] MuO-conotoxins are gating-modifier toxins that inhibit sodium current by trapping the domain II voltage sensor in the closed position to prevent opening of the sodium channel. This toxin has a preference for Nav1.4/SCN4A over Nav1.2/SCN2A sodium channels. It blocks Nav channels by interacting mainly with the C-terminal part of the pore loop of domain-3. It also blocks fast-inactivating calcium current. Blocks Nav1.8/SCN10A sodium channels and has potent and long-lasting local anesthetic effects. It can also block propagation of action potentials in A- and C-fibers in sciatic nerve as well as skeletal muscle in isolated preparations.<ref>PMID:16458302</ref> <ref>PMID:16752929</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The microO-conotoxins are an intriguing class of conotoxins targeting various voltage-dependent sodium channels and molluscan calcium channels. In the current study, we have shown MrVIA and MrVIB to be the first known peptidic inhibitors of the transient tetrodotoxin-resistant (TTX-R) Na(+) current in rat dorsal root ganglion neurons, in addition to inhibiting tetrodotoxin-sensitive Na(+) currents. Human TTX-R sodium channels are a therapeutic target for indications such as pain, highlighting the importance of the microO-conotoxins as potential leads for drug development. Furthermore, we have used NMR spectroscopy to provide the first structural information on this class of conotoxins. MrVIA and MrVIB are hydrophobic peptides that aggregate in aqueous solution but were solubilized in 50% acetonitrile/water. The three-dimensional structure of MrVIB consists of a small beta-sheet and a cystine knot arrangement of the three-disulfide bonds. It contains four backbone "loops" between successive cysteine residues that are exposed to the solvent to varying degrees. The largest of these, loop 2, is the most disordered part of the molecule, most likely due to flexibility in solution. This disorder is the most striking difference between the structures of MrVIB and the known delta- and omega-conotoxins, which along with the microO-conotoxins are members of the O superfamily. Loop 2 of omega-conotoxins has previously been shown to contain residues critical for binding to voltage-gated calcium channels, and it is interesting to speculate that the flexibility observed in MrVIB may accommodate binding to both sodium and molluscan calcium channels.

Structures of muO-conotoxins from Conus marmoreus. I nhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian sensory neurons.,Daly NL, Ekberg JA, Thomas L, Adams DJ, Lewis RJ, Craik DJ J Biol Chem. 2004 Jun 11;279(24):25774-82. Epub 2004 Mar 24. PMID:15044438<ref>PMID:15044438</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1rmk" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Conus marmoreus]]
[[Category: Large Structures]]
[[Category: Adams DJ]]
[[Category: Craik DJ]]
[[Category: Daly NL]]
[[Category: Ekberg JA]]
[[Category: Lewis RJ]]
[[Category: Thomas L]]