2y57: Difference between revisions
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==FRAGMENT GROWING INDUCES CONFORMATIONAL CHANGES IN ACETYLCHOLINE-BINDING PROTEIN: A STRUCTURAL AND THERMODYNAMIC ANALYSIS - (COMPOUND 4)== | ==FRAGMENT GROWING INDUCES CONFORMATIONAL CHANGES IN ACETYLCHOLINE-BINDING PROTEIN: A STRUCTURAL AND THERMODYNAMIC ANALYSIS - (COMPOUND 4)== | ||
<StructureSection load='2y57' size='340' side='right' caption='[[2y57]], [[Resolution|resolution]] 3.30Å' scene=''> | <StructureSection load='2y57' size='340' side='right' caption='[[2y57]], [[Resolution|resolution]] 3.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2y57]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[2y57]] is a 5 chain structure with sequence from [http://en.wikipedia.org/wiki/Aplca Aplca]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y57 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Y57 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=V37:[(1R,5S)-8-PHENETHYL-8-AZABICYCLO[3.2.1]OCTAN-3-YL]+BENZOATE'>V37</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=V37:[(1R,5S)-8-PHENETHYL-8-AZABICYCLO[3.2.1]OCTAN-3-YL]+BENZOATE'>V37</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wn9|2wn9]], [[2w8f|2w8f]], [[2xz6|2xz6]], [[2byp|2byp]], [[2xyt|2xyt]], [[2c9t|2c9t]], [[2byq|2byq]], [[2w8g|2w8g]], [[2x00|2x00]], [[2uz6|2uz6]], [[2wnl|2wnl]], [[2br8|2br8]], [[2br7|2br7]], [[2xys|2xys]], [[2xnv|2xnv]], [[2byr|2byr]], [[2xz5|2xz5]], [[2y54|2y54]], [[2byn|2byn]], [[2bys|2bys]], [[2xnt|2xnt]], [[2wnj|2wnj]], [[2w8e|2w8e]], [[2wzy|2wzy]], [[2wnc|2wnc]], [[2xnu|2xnu]], [[2y56|2y56]], [[2y58|2y58]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2wn9|2wn9]], [[2w8f|2w8f]], [[2xz6|2xz6]], [[2byp|2byp]], [[2xyt|2xyt]], [[2c9t|2c9t]], [[2byq|2byq]], [[2w8g|2w8g]], [[2x00|2x00]], [[2uz6|2uz6]], [[2wnl|2wnl]], [[2br8|2br8]], [[2br7|2br7]], [[2xys|2xys]], [[2xnv|2xnv]], [[2byr|2byr]], [[2xz5|2xz5]], [[2y54|2y54]], [[2byn|2byn]], [[2bys|2bys]], [[2xnt|2xnt]], [[2wnj|2wnj]], [[2w8e|2w8e]], [[2wzy|2wzy]], [[2wnc|2wnc]], [[2xnu|2xnu]], [[2y56|2y56]], [[2y58|2y58]]</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=2y57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y57 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2y57 RCSB], [http://www.ebi.ac.uk/pdbsum/2y57 PDBsum]</span></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=2y57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y57 OCA], [http://pdbe.org/2y57 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2y57 RCSB], [http://www.ebi.ac.uk/pdbsum/2y57 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2y57 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 2y57" style="background-color:#fffaf0;"></div> | |||
==See Also== | ==See Also== | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Aplca]] | ||
[[Category: Deesch, I J.P]] | [[Category: Deesch, I J.P]] | ||
[[Category: Edink, E]] | [[Category: Edink, E]] | ||
Revision as of 14:15, 11 August 2016
FRAGMENT GROWING INDUCES CONFORMATIONAL CHANGES IN ACETYLCHOLINE-BINDING PROTEIN: A STRUCTURAL AND THERMODYNAMIC ANALYSIS - (COMPOUND 4)FRAGMENT GROWING INDUCES CONFORMATIONAL CHANGES IN ACETYLCHOLINE-BINDING PROTEIN: A STRUCTURAL AND THERMODYNAMIC ANALYSIS - (COMPOUND 4)
Structural highlights
Publication Abstract from PubMedOptimization of fragment hits toward high-affinity lead compounds is a crucial aspect of fragment-based drug discovery (FBDD). In the current study, we have successfully optimized a fragment by growing into a ligand-inducible subpocket of the binding site of acetylcholine-binding protein (AChBP). This protein is a soluble homologue of the ligand binding domain (LBD) of Cys-loop receptors. The fragment optimization was monitored with X-ray structures of ligand complexes and systematic thermodynamic analyses using surface plasmon resonance (SPR) biosensor analysis and isothermal titration calorimetry (ITC). Using site-directed mutagenesis and AChBP from different species, we find that specific changes in thermodynamic binding profiles, are indicative of interactions with the ligand-inducible subpocket of AChBP. This study illustrates that thermodynamic analysis provides valuable information on ligand binding modes and is complementary to affinity data when guiding rational structure- and fragment-based discovery approaches. Fragment growing induces conformational changes in acetylcholine-binding protein: a structural and thermodynamic analysis.,Edink E, Rucktooa P, Retra K, Akdemir A, Nahar T, Zuiderveld O, van Elk R, Janssen E, van Nierop P, van Muijlwijk-Koezen J, Smit AB, Sixma TK, Leurs R, de Esch IJ J Am Chem Soc. 2011 Apr 13;133(14):5363-71. Epub 2011 Feb 15. PMID:21322593[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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