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/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> | <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> | ||
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==See Also== | ==See Also== | ||
*[[Acetylcholine binding protein|Acetylcholine binding protein]] | *[[Acetylcholine binding protein 3D structures|Acetylcholine binding protein 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Aplca]] | [[Category: Aplca]] | ||
[[Category: Large Structures]] | |||
[[Category: Edink, E]] | [[Category: Edink, E]] | ||
[[Category: Rucktooa, P]] | [[Category: Rucktooa, P]] | ||
Revision as of 10:23, 24 April 2019
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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