2wnl: Difference between revisions
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==CRYSTAL STRUCTURE OF APLYSIA ACHBP IN COMPLEX WITH ANABASEINE== | |||
<StructureSection load='2wnl' size='340' side='right'caption='[[2wnl]], [[Resolution|resolution]] 2.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2wnl]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Aplysia_californica Aplysia californica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2WNL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2WNL FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AN4:3,4,5,6-TETRAHYDRO-2,3-BIPYRIDINE'>AN4</scene>, <scene name='pdbligand=AN5:5-AMINO-1-PYRIDIN-3-YLPENTAN-1-ONE'>AN5</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></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=2wnl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2wnl OCA], [https://pdbe.org/2wnl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2wnl RCSB], [https://www.ebi.ac.uk/pdbsum/2wnl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2wnl ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/Q8WSF8_APLCA Q8WSF8_APLCA] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wn/2wnl_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</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=2wnl ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The pentameric acetylcholine-binding protein (AChBP) is a soluble surrogate of the ligand binding domain of nicotinic acetylcholine receptors. Agonists bind within a nest of aromatic side chains contributed by loops C and F on opposing faces of each subunit interface. Crystal structures of Aplysia AChBP bound with the agonist anabaseine, two partial agonists selectively activating the alpha7 receptor, 3-(2,4-dimethoxybenzylidene)-anabaseine and its 4-hydroxy metabolite, and an indole-containing partial agonist, tropisetron, were solved at 2.7-1.75 A resolution. All structures identify the Trp 147 carbonyl oxygen as the hydrogen bond acceptor for the agonist-protonated nitrogen. In the partial agonist complexes, the benzylidene and indole substituent positions, dictated by tight interactions with loop F, preclude loop C from adopting the closed conformation seen for full agonists. Fluctuation in loop C position and duality in ligand binding orientations suggest molecular bases for partial agonism at full-length receptors. This study, while pointing to loop F as a major determinant of receptor subtype selectivity, also identifies a new template region for designing alpha7-selective partial agonists to treat cognitive deficits in mental and neurodegenerative disorders. | |||
Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal alpha7 nicotinic acetylcholine receptor.,Hibbs RE, Sulzenbacher G, Shi J, Talley TT, Conrod S, Kem WR, Taylor P, Marchot P, Bourne Y EMBO J. 2009 Oct 7;28(19):3040-51. Epub 2009 Aug 20. PMID:19696737<ref>PMID:19696737</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2wnl" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
*[[Acetylcholine binding protein|Acetylcholine binding protein]] | *[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Aplysia californica]] | [[Category: Aplysia californica]] | ||
[[Category: Bourne | [[Category: Large Structures]] | ||
[[Category: Conrod | [[Category: Bourne Y]] | ||
[[Category: Hibbs | [[Category: Conrod S]] | ||
[[Category: Kem | [[Category: Hibbs R]] | ||
[[Category: Marchot | [[Category: Kem W]] | ||
[[Category: Shi | [[Category: Marchot P]] | ||
[[Category: Sulzenbacher | [[Category: Shi J]] | ||
[[Category: Talley | [[Category: Sulzenbacher G]] | ||
[[Category: Taylor | [[Category: Talley T]] | ||
[[Category: Taylor P]] | |||
Latest revision as of 19:04, 13 December 2023
CRYSTAL STRUCTURE OF APLYSIA ACHBP IN COMPLEX WITH ANABASEINECRYSTAL STRUCTURE OF APLYSIA ACHBP IN COMPLEX WITH ANABASEINE
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe pentameric acetylcholine-binding protein (AChBP) is a soluble surrogate of the ligand binding domain of nicotinic acetylcholine receptors. Agonists bind within a nest of aromatic side chains contributed by loops C and F on opposing faces of each subunit interface. Crystal structures of Aplysia AChBP bound with the agonist anabaseine, two partial agonists selectively activating the alpha7 receptor, 3-(2,4-dimethoxybenzylidene)-anabaseine and its 4-hydroxy metabolite, and an indole-containing partial agonist, tropisetron, were solved at 2.7-1.75 A resolution. All structures identify the Trp 147 carbonyl oxygen as the hydrogen bond acceptor for the agonist-protonated nitrogen. In the partial agonist complexes, the benzylidene and indole substituent positions, dictated by tight interactions with loop F, preclude loop C from adopting the closed conformation seen for full agonists. Fluctuation in loop C position and duality in ligand binding orientations suggest molecular bases for partial agonism at full-length receptors. This study, while pointing to loop F as a major determinant of receptor subtype selectivity, also identifies a new template region for designing alpha7-selective partial agonists to treat cognitive deficits in mental and neurodegenerative disorders. Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal alpha7 nicotinic acetylcholine receptor.,Hibbs RE, Sulzenbacher G, Shi J, Talley TT, Conrod S, Kem WR, Taylor P, Marchot P, Bourne Y EMBO J. 2009 Oct 7;28(19):3040-51. Epub 2009 Aug 20. PMID:19696737[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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