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1niy

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THREE DIMENSIONAL SOLUTION STRUCTURE OF HAINANTOXIN-IV BY 2D 1H-NMR

Structural highlights

1niy is a 1 chain structure with sequence from Haplopelma hainanum. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

H4A01_CYRHA Neurotoxin that selectively inhibits neuronal tetrodotoxin-sensitive voltage-gated sodium channels (Nav) (IC(50)=44.6 nM) (PubMed:14512091, PubMed:12518233). It is active on Nav1.2/SCN2A (IC(50)=22.4 nM), Nav1.6/SCN8A (IC(50)=50.1 nM) and Nav1.7/SCN9A (IC(50)=48.9 nM) (PubMed:29703751). It shows low affinity for lipid bilayers (PubMed:29703751).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Hainantoxin-IV (HNTX-IV) can specifically inhibit the neuronal tetrodotoxin-sensitive sodium channels and defines a new class of depressant spider toxin. The sequence of native HNTX-IV is ECLGFGKGCNPSNDQCCKSSNLVCSRKHRWCKYEI-NH(2). In the present study, to obtain further insight into the primary and tertiary structural requirements of neuronal sodium channel blockers, we determined the solution structure of HNTX-IV as a typical inhibitor cystine knot motif and synthesized four mutants designed based on the predicted sites followed by structural elucidation of two inactive mutants. Pharmacological studies indicated that the S12A and R26A mutants had activities near that of native HNTX-IV, while K27A and R29A demonstrated activities reduced by 2 orders of magnitude. (1)H MR analysis showed the similar molecular conformations for native HNTX-IV and four synthetic mutants. Furthermore, in the determined structures of K27A and R29A, the side chains of residues 27 and 29 were located in the identical spatial position to those of native HNTX-IV. These results suggested that residues Ser(12), Arg(26), Lys(27), and Arg(29) were not responsible for stabilizing the distinct conformation of HNTX-IV, but Lys(27) and Arg(29) were critical for the bioactivities. The potency reductions produced by Ala substitutions were primarily due to the direct interaction of the essential residues Lys(27) and Arg(29) with sodium channels rather than to a conformational change. After comparison of these structures and activities with correlated toxins, we hypothesized that residues Lys(27), Arg(29), His(28), Lys(32), Phe(5), and Trp(30) clustered on one face of HNTX-IV were responsible for ligand binding.

Structure--activity relationships of hainantoxin-IV and structure determination of active and inactive sodium channel blockers.,Li D, Xiao Y, Xu X, Xiong X, Lu S, Liu Z, Zhu Q, Wang M, Gu X, Liang S J Biol Chem. 2004 Sep 3;279(36):37734-40. Epub 2004 Jun 16. PMID:15201273^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Xiao YC, Liang SP. Inhibition of sodium channels in rat dorsal root ganglion neurons by Hainantoxin-IV, a novel spider toxin. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 2003 Jan;35(1):82-5 PMID:12518233
↑ Liu Z, Dai J, Chen Z, Hu W, Xiao Y, Liang S. Isolation and characterization of hainantoxin-IV, a novel antagonist of tetrodotoxin-sensitive sodium channels from the Chinese bird spider Selenocosmia hainana. Cell Mol Life Sci. 2003 May;60(5):972-8. PMID:12827284 doi:10.1007/s00018-003-2354-x
↑ Xiao Y, Liang S. Inhibition of neuronal tetrodotoxin-sensitive Na+ channels by two spider toxins: hainantoxin-III and hainantoxin-IV. Eur J Pharmacol. 2003 Sep 5;477(1):1-7. PMID:14512091 doi:10.1016/s0014-2999(03)02190-3
↑ Agwa AJ, Peigneur S, Chow CY, Lawrence N, Craik DJ, Tytgat J, King GF, Henriques ST, Schroeder CI. Gating modifier toxins isolated from spider venom: modulation of voltage-gated sodium channels and the role of lipid membranes. J Biol Chem. 2018 Apr 27. pii: RA118.002553. doi: 10.1074/jbc.RA118.002553. PMID:29703751 doi:http://dx.doi.org/10.1074/jbc.RA118.002553
↑ Li D, Xiao Y, Xu X, Xiong X, Lu S, Liu Z, Zhu Q, Wang M, Gu X, Liang S. Structure--activity relationships of hainantoxin-IV and structure determination of active and inactive sodium channel blockers. J Biol Chem. 2004 Sep 3;279(36):37734-40. Epub 2004 Jun 16. PMID:15201273 doi:10.1074/jbc.M405765200

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1niy"

Categories: Haplopelma hainanum | Large Structures | Gu X | Li D | Liang S | Lu S

@@ Line 1: / Line 1: @@
 ==THREE DIMENSIONAL SOLUTION STRUCTURE OF HAINANTOXIN-IV BY 2D 1H-NMR==
-<StructureSection load='1niy' size='340' side='right' caption='[[1niy]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
+<StructureSection load='1niy' size='340' side='right'caption='[[1niy]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[1niy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Haplopelma_hainanum Haplopelma hainanum]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NIY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1NIY FirstGlance]. <br>
+<table><tr><td colspan='2'>[[1niy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Haplopelma_hainanum Haplopelma hainanum]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NIY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1NIY FirstGlance]. <br>
-</td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene></td></tr>
+</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1niy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1niy OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1niy RCSB], [http://www.ebi.ac.uk/pdbsum/1niy PDBsum]</span></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=1niy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1niy OCA], [https://pdbe.org/1niy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1niy RCSB], [https://www.ebi.ac.uk/pdbsum/1niy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1niy ProSAT]</span></td></tr>
 </table>
+== Function ==
+[https://www.uniprot.org/uniprot/H4A01_CYRHA H4A01_CYRHA] Neurotoxin that selectively inhibits neuronal tetrodotoxin-sensitive voltage-gated sodium channels (Nav) (IC(50)=44.6 nM) (PubMed:14512091, PubMed:12518233). It is active on Nav1.2/SCN2A (IC(50)=22.4 nM), Nav1.6/SCN8A (IC(50)=50.1 nM) and Nav1.7/SCN9A (IC(50)=48.9 nM) (PubMed:29703751). It shows low affinity for lipid bilayers (PubMed:29703751).<ref>PMID:12518233</ref> <ref>PMID:12827284</ref> <ref>PMID:14512091</ref> <ref>PMID:29703751</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 14: / Line 17: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 1niy" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>
@@ Line 19: / Line 23: @@
 </StructureSection>
 [[Category: Haplopelma hainanum]]
-[[Category: Gu, X]]
+[[Category: Large Structures]]
-[[Category: Li, D]]
+[[Category: Gu X]]
-[[Category: Liang, S]]
+[[Category: Li D]]
-[[Category: Lu, S]]
+[[Category: Liang S]]
-[[Category: Inhibitor cystine knot motif]]
+[[Category: Lu S]]
-[[Category: Neurotoxin]]
-[[Category: Toxin]]

1niy

From Proteopedia

Current revision

THREE DIMENSIONAL SOLUTION STRUCTURE OF HAINANTOXIN-IV BY 2D 1H-NMR

Structural highlights

Function

Publication Abstract from PubMed

References

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