2y57

Fragment growing induces conformational changes in acetylcholine- binding protein: A structural and thermodynamic analysis - (Compound 4)

spinqualitylabelsall models 2y57, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2y57 is a 5 chain structure with sequence from Aplca. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, SO4, V37 Related: 2wn9, 2w8f, 2xz6, 2byp, 2xyt, 2c9t, 2byq, 2w8g, 2x00, 2uz6, 2wnl, 2br8, 2br7, 2xys, 2xnv, 2byr, 2xz5, 2y54, 2byn, 2bys, 2xnt, 2wnj, 2w8e, 2wzy, 2wnc, 2xnu, 2y56, 2y58 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Optimization 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholine binding protein 3D structures

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