View source for 2n6o


==Structure of spider-venom peptide Hm1a==
<StructureSection load='2n6o' size='340' side='right'caption='[[2n6o]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2n6o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Heteroscodra_maculata Heteroscodra maculata]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2N6O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2N6O FirstGlance]. <br>
</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=2n6o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2n6o OCA], [https://pdbe.org/2n6o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2n6o RCSB], [https://www.ebi.ac.uk/pdbsum/2n6o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2n6o ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TX1A_HETMC TX1A_HETMC] Gating-modifier toxin that potently inhibits inactivation of the mammalian Nav1.1/SCN1A sodium channel (EC(50)=38 nM) (PubMed:27281198, PubMed:30076230). Also moderately inhibits inactivation of Nav1.2/SCN2A (EC(50)=236 nM) and Nav1.3/SCN3A (EC(50)=220 nM) when the channels are expressed in oocytes without the beta-1 auxiliary subunit (PubMed:27281198). Does not inhibit inactivation of Nav1.2/SCN2A when the channel is coexpressed with the beta-1 auxiliary subunit (PubMed:30076230). When tested on Nav1.1/SCN1A channel, it enhances peak current amplitude and potently delays channel inactivation in a dose-dependent manner, leading to a large sustained current (PubMed:30076230). It has no effect on the voltage-dependence of steady-state activation, and induces a depolarizing shift in the voltage dependence of inactivation (PubMed:30076230). In addition, it does not modify the recovery from fast inactivation in Nav1.1/SCN1A (PubMed:30076230). The binding affinity and subtype selectivity of the toxin towards Nav1.1/SCN1A channel is determined by residues within both the S1-S2 and S3-S4 loops of the domain IV voltage sensor of the channel (PubMed:27281198). This toxin also weakly inhibits several subtypes of voltage-gated potassium channels (PubMed:27281198). It moderately blocks Kv2.1/KCNB1 (23% inhibition at 100 nM), Kv2.2/KCNB2 (19.7% at 100 nM and 51% at 300 nM), Kv4.1/KCND1 (IC(50)=280 nM), Kv4.2/KCND2 (39% at 300 nM) and Kv4.3/KCND3 (43% at 300 nM) (PubMed:12065754). In vivo, intracerebroventricular injection into mice elicits convulsions, spasms, tremors and rapid death (PubMed:12065754). When injected into mouse hindpaw, the toxin elicits an immediate and robust response to pain (PubMed:27281198). However, intraplantar injection of toxin does not cause neurogenic inflammation or alter sensitivity to heat, indicative of a modality-specific effect on mechanosensitive neurons (PubMed:27281198). In Dravet syndrome mice model, intracerebroventricular infusion of this peptide rescues mice from seizures and premature death (PubMed:30076230).<ref>PMID:12065754</ref> <ref>PMID:27281198</ref> <ref>PMID:30076230</ref> 
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Heteroscodra maculata]]
[[Category: Large Structures]]
[[Category: King GF]]
[[Category: Mobli M]]
[[Category: Undheim EAB]]