This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


1lxh

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (08:29, 10 April 2024) (edit) (undo)
 
(11 intermediate revisions not shown.)
Line 1: Line 1:
-
[[Image:1lxh.gif|left|200px]]
 
-
<!--
+
==Solution structure of alpha-cobratoxin complexed with a cognate peptide (minimized average structure)==
-
The line below this paragraph, containing "STRUCTURE_1lxh", creates the "Structure Box" on the page.
+
<StructureSection load='1lxh' size='340' side='right'caption='[[1lxh]]' scene=''>
-
You may change the PDB parameter (which sets the PDB file loaded into the applet)
+
== Structural highlights ==
-
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+
<table><tr><td colspan='2'>[[1lxh]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Naja_kaouthia Naja kaouthia] and [https://en.wikipedia.org/wiki/Tetronarce_californica Tetronarce californica]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1LXH FirstGlance]. <br>
-
or leave the SCENE parameter empty for the default display.
+
</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HSL:HOMOSERINE+LACTONE'>HSL</scene></td></tr>
-
{{STRUCTURE_1lxh| PDB=1lxh | SCENE= }}
+
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1lxh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lxh OCA], [https://pdbe.org/1lxh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1lxh RCSB], [https://www.ebi.ac.uk/pdbsum/1lxh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1lxh ProSAT]</span></td></tr>
-
 
+
</table>
-
'''Solution structure of alpha-cobratoxin complexed with a cognate peptide (minimized average structure)'''
+
== Function ==
-
 
+
[https://www.uniprot.org/uniprot/3L21_NAJKA 3L21_NAJKA] Monomer: binds with high affinity to muscular (alpha-1-beta-1-gamma-delta/CHRNA1-CHRNB1-CHRNG-CHRND) nAChR (tested on Torpedo californica, Kd=0.2-4.5 nM) and neuronal alpha-7/CHRNA7 nicotinic acetylcholine receptors (Kd=13-105 nM) (PubMed:18381281, PubMed:9305882, PubMed:22223648). Also inhibits GABA(A) channels (PubMed:26221036). Heteropentamer targets studied are composed of alpha-1-beta-3-gamma-2 (GABRA1-GABRB3-GABRG2) subunits (IC(50)=236 nM), alpha-1-beta-2-gamma-2 (GABRA1-GABRB2-GABRG2) subunits (IC(50)=469 nM), alpha-2-beta-2-gamma-2 (GABRA2-GABRB2-GABRG2) subunits (IC(50)=485 nM), alpha-5-beta-3-gamma-2 (GABRA5-GABRB3-GABRG2) subunits (IC(50)=635 nM), and alpha-2-beta-3-gamma-2 (GABRA2-GABRB3-GABRG2) subunits (IC(50)=1099 nM) (activated by 10 uM GABA) (PubMed:26221036).<ref>PMID:18381281</ref> <ref>PMID:22223648</ref> <ref>PMID:26221036</ref> <ref>PMID:30025921</ref> Homodimer: binds with high affinity (but lower than the monomeric form) to muscular (IC(50)=9.7 nM) and with low affinity to neuronal alpha-7/CHRNA7 nAChRs (IC(50)=1370 nM) (PubMed:22223648). However, it acquires (compared to the monomeric form) the capacity to block alpha-3/beta-2 (CHRNA3/CHRNB2) nAChRs (PubMed:18381281).<ref>PMID:18381281</ref> <ref>PMID:22223648</ref> Heterodimer with cytotoxin 3 (AC P01446): is slightly more active than the homodimer in inhibiting alpha-7/CHRNA7 nAChR and is considerably more active in blocking the alpha-3-beta-2/CHRNA3-CHRNB2 nAChR.<ref>PMID:22223648</ref>
-
 
+
== Evolutionary Conservation ==
-
==Overview==
+
[[Image:Consurf_key_small.gif|200px|right]]
-
The alpha18-mer peptide, spanning residues 181-198 of the Torpedo nicotinic acetylcholine receptor alpha1 subunit, contains key binding determinants for agonists and competitive antagonists. To investigate whether the alpha18-mer can bind other alpha-neurotoxins besides alpha-bungarotoxin, we designed a two-dimensional (1)H-(15)N heteronuclear single quantum correlation experiment to screen four related neurotoxins for their binding ability to the peptide. Of the four toxins tested (erabutoxin a, erabutoxin b, LSIII, and alpha-cobratoxin), only alpha-cobratoxin binds the alpha18-mer to form a 1:1 complex. The NMR solution structure of the alpha-cobratoxin.alpha18-mer complex was determined with a backbone root mean square deviation of 1.46 A. In the structure, alpha-cobratoxin contacts the alpha18-mer at the tips of loop I and II and through C-terminal cationic residues. The contact zone derived from the intermolecular nuclear Overhauser effects is in agreement with recent biochemical data. Furthermore, the structural models support the involvement of cation-pi interactions in stabilizing the complex. In addition, the binding screen results suggest that C-terminal cationic residues of alpha-bungarotoxin and alpha-cobratoxin contribute significantly to binding of the alpha18-mer. Finally, we present a structural model for nicotinic acetylcholine receptor-alpha-cobratoxin interaction by superimposing the alpha-cobratoxin.alpha18-mer complex onto the crystal structure of the acetylcholine-binding protein (Protein Data Bank code ).
+
Check<jmol>
-
 
+
<jmolCheckbox>
-
==About this Structure==
+
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/lx/1lxh_consurf.spt"</scriptWhenChecked>
-
1LXH is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Naja_kaouthia Naja kaouthia] and [http://en.wikipedia.org/wiki/Torpedo_californica Torpedo californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1LXH OCA].
+
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
-
 
+
<text>to colour the structure by Evolutionary Conservation</text>
-
==Reference==
+
</jmolCheckbox>
-
NMR-based binding screen and structural analysis of the complex formed between alpha-cobratoxin and an 18-mer cognate peptide derived from the alpha 1 subunit of the nicotinic acetylcholine receptor from Torpedo californica., Zeng H, Hawrot E, J Biol Chem. 2002 Oct 4;277(40):37439-45. Epub 2002 Jul 19. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12133834 12133834]
+
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1lxh ConSurf].
 +
<div style="clear:both"></div>
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Large Structures]]
[[Category: Naja kaouthia]]
[[Category: Naja kaouthia]]
-
[[Category: Protein complex]]
+
[[Category: Tetronarce californica]]
-
[[Category: Torpedo californica]]
+
[[Category: Hawrot E]]
-
[[Category: Hawrot, E.]]
+
[[Category: Zeng H]]
-
[[Category: Zeng, H.]]
+
-
[[Category: Nicotinic acetylcholine receptor]]
+
-
[[Category: Protein-protein interaction]]
+
-
[[Category: Toxin,alpha-cobratoxin]]
+
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 00:23:56 2008''
+

Current revision

Solution structure of alpha-cobratoxin complexed with a cognate peptide (minimized average structure)

PDB ID 1lxh

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/1lxh"
Personal tools