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| | ==Solution NMR Structure of a Long Neurotoxin from the Venom of the Asian Cobra, 20 Structures== | | ==Solution NMR Structure of a Long Neurotoxin from the Venom of the Asian Cobra, 20 Structures== |
| - | <StructureSection load='1w6b' size='340' side='right'caption='[[1w6b]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='1w6b' size='340' side='right'caption='[[1w6b]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1w6b]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Naja_oxiana Naja oxiana]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W6B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1W6B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1w6b]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Naja_oxiana Naja oxiana]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1W6B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1W6B FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1ntn|1ntn]]</td></tr> | + | </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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1w6b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w6b OCA], [http://pdbe.org/1w6b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1w6b RCSB], [http://www.ebi.ac.uk/pdbsum/1w6b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1w6b ProSAT]</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=1w6b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1w6b OCA], [https://pdbe.org/1w6b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1w6b RCSB], [https://www.ebi.ac.uk/pdbsum/1w6b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1w6b ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NXL1_NAJOX NXL1_NAJOX]] Binds with high affinity to muscular and neuronal alpha-7 nicotinic acetylcholine receptors (nAChRs).<ref>PMID:9305882</ref> | + | [https://www.uniprot.org/uniprot/3L21_NAJOX 3L21_NAJOX] Binds with high affinity to muscular (tested on Torpedo marmorata AChR, Kd=0.38 nM) and neuronal (tested on chimeric alpha-7/CHRNA7, Kd=12 nM) nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular and neuronal transmission (PubMed:9305882). The toxin also shows a very weak inhibition of GABA(A) receptors composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) subunits (PubMed:26221036).<ref>PMID:26221036</ref> <ref>PMID:9305882</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Naja oxiana]] | | [[Category: Naja oxiana]] |
| - | [[Category: Amininasab, M]] | + | [[Category: Amininasab M]] |
| - | [[Category: Elmi, M M]] | + | [[Category: Elmi MM]] |
| - | [[Category: Naderi-Manesh, H]] | + | [[Category: Naderi-Manesh H]] |
| - | [[Category: Sarbolouki, M N]] | + | [[Category: Sarbolouki MN]] |
| - | [[Category: Talebzadeh-Farooji, M]] | + | [[Category: Talebzadeh-Farooji M]] |
| - | [[Category: Long neurotoxin]]
| + | |
| - | [[Category: Toxin]]
| + | |
| - | [[Category: Venom]]
| + | |
| Structural highlights
Function
3L21_NAJOX Binds with high affinity to muscular (tested on Torpedo marmorata AChR, Kd=0.38 nM) and neuronal (tested on chimeric alpha-7/CHRNA7, Kd=12 nM) nicotinic acetylcholine receptor (nAChR) and inhibits acetylcholine from binding to the receptor, thereby impairing neuromuscular and neuronal transmission (PubMed:9305882). The toxin also shows a very weak inhibition of GABA(A) receptors composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) subunits (PubMed:26221036).[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The NMR solution structures of NTX-1 (PDB code 1W6B and BMRB 6288), a long neurotoxin isolated from the venom of Naja naja oxiana, and the molecular dynamics simulation of these structures are reported. Calculations are based on 1114 NOEs, 19 hydrogen bonds, 19 dihedral angle restraints and secondary chemical shifts derived from 1H to 13C HSQC spectrum. Similar to other long neurotoxins, the three-finger like structure shows a double and a triple stranded beta-sheet as well as some flexible regions, particularly at the tip of loop II and the C-terminal tail. The solution NMR and molecular dynamics simulated structures are in good agreement with root mean square deviation values of 0.23 and 1 A for residues involved in beta-sheet regions, respectively. The overall fold in the NMR structure is similar to that of the X-ray crystallography, although some differences exist in loop I and the tip of loop II. The most functionally important residues are located at the tip of loop II and it appears that the mobility and the local structure in this region modulate the binding of NTX-1 and other long neurotoxins to the nicotinic acetylcholine receptor.
Solution structure of long neurotoxin NTX-1 from the venom of Naja naja oxiana by 2D-NMR spectroscopy.,Talebzadeh-Farooji M, Amininasab M, Elmi MM, Naderi-Manesh H, Sarbolouki MN Eur J Biochem. 2004 Dec;271(23-24):4950-7. PMID:15606783[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kudryavtsev DS, Shelukhina IV, Son LV, Ojomoko LO, Kryukova EV, Lyukmanova EN, Zhmak MN, Dolgikh DA, Ivanov IA, Kasheverov IE, Starkov VG, Ramerstorfer J, Sieghart W, Tsetlin VI, Utkin YN. Neurotoxins from snake venoms and α-conotoxin ImI inhibit functionally active ionotropic γ-aminobutyric acid (GABA) receptors. J Biol Chem. 2015 Sep 11;290(37):22747-58. PMID:26221036 doi:10.1074/jbc.M115.648824
- ↑ Servent D, Winckler-Dietrich V, Hu HY, Kessler P, Drevet P, Bertrand D, Menez A. Only snake curaremimetic toxins with a fifth disulfide bond have high affinity for the neuronal alpha7 nicotinic receptor. J Biol Chem. 1997 Sep 26;272(39):24279-86. PMID:9305882
- ↑ Talebzadeh-Farooji M, Amininasab M, Elmi MM, Naderi-Manesh H, Sarbolouki MN. Solution structure of long neurotoxin NTX-1 from the venom of Naja naja oxiana by 2D-NMR spectroscopy. Eur J Biochem. 2004 Dec;271(23-24):4950-7. PMID:15606783 doi:10.1111/j.1432-1033.2004.04465.x
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