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3zdg
From Proteopedia
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| - | + | ==Crystal Structure of Ls-AChBP complexed with carbamoylcholine analogue 3-(dimethylamino)butyl dimethylcarbamate (DMABC)== | |
| - | + | <StructureSection load='3zdg' size='340' side='right' caption='[[3zdg]], [[Resolution|resolution]] 2.48Å' scene=''> | |
| - | + | == Structural highlights == | |
| + | <table><tr><td colspan='2'>[[3zdg]] is a 20 chain structure with sequence from [http://en.wikipedia.org/wiki/Lymnaea_stagnalis Lymnaea stagnalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZDG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZDG FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1PE:PENTAETHYLENE+GLYCOL'>1PE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=XRX:3-(DIMETHYLAMINO)BUTYL+DIMETHYLCARBAMATE'>XRX</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3zdh|3zdh]]</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=3zdg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zdg OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zdg RCSB], [http://www.ebi.ac.uk/pdbsum/3zdg PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | In our search for selective agonists for the alpha(4)beta(2) subtype of the nicotinic acetylcholine receptors (nAChRs), we have synthesized and characterized a series of novel heterocyclic analogues of 3-(dimethylamino)butyl dimethylcarbamate (DMABC, 4). All new heterocyclic analogues, especially N,N-dimethyl-4-(1-methyl-1H-imidazol-2-yloxy)butan-2-amine (7), showed an improved binding selectivity profile in favor of alpha(4)beta(2) over other nAChR subtypes, primarily due to impaired binding at beta(4) containing receptors. This observation can be rationalized based on cocrystal structures of (R)-4 and (R)-7 bound to acetylcholine binding protein from Lymnaea stagnalis. Functional characterization at both (alpha(4))(2)(beta(2))(3) and (alpha(4))(3)(beta(2))(2) receptors using two-electrode voltage clamp techniques in Xenopus laevis oocytes indicates that the investigated compounds interact differently with the two receptor stoichiometries. Compound 7 is an efficacious agonist at both alpha(4)-beta(2) and alpha(4)-alpha(4) binding sites, while the close analogue N,N-dimethyl-4-(1,4-dimethyl-1H-imidazol-2-yloxy)butan-2-amine (9) primarily activates via alpha(4)-beta(2) binding sites. The results suggest that it may be possible to rationally design compounds with specific stoichiometry preferences. | ||
| - | + | Synthesis, Pharmacology, and Biostructural Characterization of Novel alpha(4)beta(2) Nicotinic Acetylcholine Receptor Agonists.,Ussing CA, Hansen CP, Petersen JG, Jensen AA, Rohde LA, Ahring PK, Nielsen EO, Kastrup JS, Gajhede M, Frolund B, Balle T J Med Chem. 2013 Feb 14;56(3):940-51. doi: 10.1021/jm301409f. Epub 2013 Jan 22. PMID:23256554<ref>PMID:23256554</ref> | |
| - | + | ||
| - | == | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[ | + | </div> |
| + | |||
| + | ==See Also== | ||
| + | *[[Acetylcholine binding protein|Acetylcholine binding protein]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Lymnaea stagnalis]] | [[Category: Lymnaea stagnalis]] | ||
| - | [[Category: Ahring, P K | + | [[Category: Ahring, P K]] |
| - | [[Category: Balle, T | + | [[Category: Balle, T]] |
| - | [[Category: Frolund, B | + | [[Category: Frolund, B]] |
| - | [[Category: Gajhede, M | + | [[Category: Gajhede, M]] |
| - | [[Category: Hansen, C P | + | [[Category: Hansen, C P]] |
| - | [[Category: Jensen, A A | + | [[Category: Jensen, A A]] |
| - | [[Category: Kastrup, J S | + | [[Category: Kastrup, J S]] |
| - | [[Category: Nielsen, E O | + | [[Category: Nielsen, E O]] |
| - | [[Category: Petersen, J G | + | [[Category: Petersen, J G]] |
| - | [[Category: Rohde, L A.H | + | [[Category: Rohde, L A.H]] |
| - | [[Category: Ussing, C A | + | [[Category: Ussing, C A]] |
[[Category: Acetylcholine-binding protein]] | [[Category: Acetylcholine-binding protein]] | ||
Revision as of 09:54, 21 December 2014
Crystal Structure of Ls-AChBP complexed with carbamoylcholine analogue 3-(dimethylamino)butyl dimethylcarbamate (DMABC)
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