4b5d
From Proteopedia
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| - | [[ | + | ==Capitella teleta AChBP in complex with psychonicline (3-((2(S)- Azetidinyl)methoxy)-5-((1S,2R)-2-(2-hydroxyethyl)cyclopropyl)pyridine)== |
| + | <StructureSection load='4b5d' size='340' side='right' caption='[[4b5d]], [[Resolution|resolution]] 2.19Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4b5d]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Capitella_teleta Capitella teleta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4B5D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4B5D FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SW4:2-[(1R,2S)-2-[5-[[(2S)-AZETIDIN-2-YL]METHOXY]PYRIDIN-3-YL]CYCLOPROPYL]ETHANOL'>SW4</scene></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=4b5d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4b5d OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4b5d RCSB], [http://www.ebi.ac.uk/pdbsum/4b5d PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Structure-based drug design can potentially accelerate the development of new therapeutics. In this study, a cocrystal structure of the acetylcholine binding protein (AChBP) from Capitella teleta (Ct) in complex with a cyclopropane-containing selective alpha4beta2-nicotinic acetylcholine receptor (nAChR) partial agonist (compound 5) was acquired. The structural determinants required for ligand binding obtained from this AChBP X-ray structure were used to refine a previous model of the human alpha4beta2-nAChR, thus possibly providing a better understanding of the structure of the human receptor. To validate the potential application of the structure of the Ct-AChBP in the engineering of new alpha4beta2-nAChR ligands, homology modeling methods, combined with in silico ADME calculations, were used to design analogues of compound 5. The most promising compound, 12, exhibited an improved metabolic stability in comparison to the parent compound 5 while retaining favorable pharmacological parameters together with appropriate behavioral end points in the rodent studies. | ||
| - | + | Insights into the Structural Determinants Required for High-Affinity Binding of Chiral Cyclopropane-Containing Ligands to alpha4beta2-Nicotinic Acetylcholine Receptors: An Integrated Approach to Behaviorally Active Nicotinic Ligands.,Zhang HK, Eaton JB, Yu LF, Nys M, Mazzolari A, van Elk R, Smit AB, Alexandrov V, Hanania T, Sabath E, Fedolak A, Brunner D, Lukas RJ, Vistoli G, Ulens C, Kozikowski AP J Med Chem. 2012 Sep 7. PMID:22928944<ref>PMID:22928944</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| - | + | <references/> | |
| - | == | + | __TOC__ |
| - | + | </StructureSection> | |
[[Category: Capitella teleta]] | [[Category: Capitella teleta]] | ||
| - | [[Category: Nys, M | + | [[Category: Nys, M]] |
| - | [[Category: Ulens, C | + | [[Category: Ulens, C]] |
[[Category: Acetylcholine-binding protein]] | [[Category: Acetylcholine-binding protein]] | ||
[[Category: Ion channel]] | [[Category: Ion channel]] | ||
[[Category: Nicotinic receptor]] | [[Category: Nicotinic receptor]] | ||
Revision as of 14:04, 4 January 2015
Capitella teleta AChBP in complex with psychonicline (3-((2(S)- Azetidinyl)methoxy)-5-((1S,2R)-2-(2-hydroxyethyl)cyclopropyl)pyridine)
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