4dbm

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4dbm]] is a 5 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=4DBM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DBM FirstGlance]. <br>
<table><tr><td colspan='2'>[[4dbm]] is a 5 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=4DBM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DBM FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0J0:(3-EXO)-8,8-DIMETHYL-3-(4-{[(1-METHYL-2-OXO-1,2-DIHYDROQUINOLIN-4-YL)OXY]METHYL}-1H-1,2,3-TRIAZOL-1-YL)-8-AZONIABICYCLO[3.2.1]OCTANE'>0J0</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0J0:(3-EXO)-8,8-DIMETHYL-3-(4-{[(1-METHYL-2-OXO-1,2-DIHYDROQUINOLIN-4-YL)OXY]METHYL}-1H-1,2,3-TRIAZOL-1-YL)-8-AZONIABICYCLO[3.2.1]OCTANE'>0J0</scene>, <scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=4dbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dbm OCA], [https://pdbe.org/4dbm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dbm RCSB], [https://www.ebi.ac.uk/pdbsum/4dbm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dbm 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=4dbm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4dbm OCA], [https://pdbe.org/4dbm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4dbm RCSB], [https://www.ebi.ac.uk/pdbsum/4dbm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4dbm ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/Q8WSF8_APLCA Q8WSF8_APLCA]]
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[https://www.uniprot.org/uniprot/Q8WSF8_APLCA Q8WSF8_APLCA]
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Nicotinic acetylcholine receptors (nAChRs), being responsible for mediating key physiological functions, are ubiquitous in the central and peripheral nervous systems. As members of the Cys loop ligand-gated ion channel family, neuronal nAChRs are pentameric, composed of various permutations of alpha (alpha2 to alpha10) and beta (beta2 to beta4) subunits forming functional heteromeric or homomeric receptors. Diversity in nAChR subunit composition complicates development of selective ligands for specific subtypes, since the five binding sites reside at the subunit interfaces. The acetylcholine binding protein (AChBP), a soluble extracellular domain homologue secreted by mollusks, serves as a general structural surrogate for the nAChRs. In this work, homomeric AChBPs from Lymnaea and Aplysia snails were used as in situ templates for the generation of novel and potent ligands that selec-tively bind to these proteins. The cycloaddition reaction between building block azides and alkynes to form stable 1,2,3-triazoles generated the leads. The extent of triazole formation on the AChBP template correlated with the affinity of the triazole product at the nicotinic ligand binding site. Instead of the in situ protein-templated azide-alkyne cycloaddition reaction occurring at a local-ized, sequestered enzyme active center as previously shown, we demonstrate that the in situ reaction can take place at subunit inter-faces of an oligomeric protein and can thus be used as a tool for identification of novel candidate nAChR ligands. The crystal struc-ture of one of the in situ formed triazole-AChBP complexes shows binding poses and molecular determinants of interactions pre-dicted from structures of known agonists and antagonists. Hence, the click chemistry approach with an in situ template of a receptor provides a novel synthetic avenue for generating candidate agonists and antagonists for ligand-gated ion channels.
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Generation of Candidate Ligands for Nicotinic Acetylcholine Receptors via In Situ Click Chemistry with a Soluble Acetylcholine Binding Protein Template.,Grimster NP, Stump B, Fotsing JR, Weide T, Talley TT, Yamauchi JG, Nemecz A, Kim C, Ho KY, Sharpless KB, Taylor P, Fokin VV J Am Chem Soc. 2012 Mar 6. PMID:22394239<ref>PMID:22394239</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4dbm" style="background-color:#fffaf0;"></div>
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==See Also==
==See Also==
*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]]
*[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]]
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== References ==
 
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<references/>
 
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</StructureSection>
</StructureSection>

Revision as of 14:30, 14 March 2024

Aplysia californica-AChBP in complex with triazole 18

PDB ID 4dbm

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