4qac | pdb_00004qac

X-RAY STRUCTURE OF ACETYLCHOLINE BINDING PROTEIN (ACHBP) IN COMPLEX WITH 4-(4-methylpiperidin-1-yl)-6-(4-(trifluoromethyl)phenyl)pyrimidin-2-amine

spinqualitylabelsall models 4qac, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4qac is a 10 chain structure with sequence from Lymnaea stagnalis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: KK3, NAG, PO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ACHP_LYMST Binds to acetylcholine. Modulates neuronal synaptic transmission. Publication Abstract from PubMed The nicotinic acetylcholine receptor (nAChR) and the acetylcholine binding protein (AChBP) are pentameric oligomers in which binding sites for nicotinic agonists and competitive antagonists are found at selected subunit interfaces. The nAChR spontaneously exists in multiple conformations associated with its activation and desensitization steps, and conformations are selectively stabilized by binding of agonists and antagonists. In the nAChR, agonist binding and the associated conformational changes accompanying activation and desensitization are cooperative. AChBP, which lacks the transmembrane spanning and cytoplasmic domains, serves as a homology model of the extracellular domain of the nAChRs. We identified unique cooperative binding behavior of a number of 4,6-disubstituted 2-aminopyrimidines to Lymnaea AChBP, with different molecular variants exhibiting positive, nH > 1.0, and negative cooperativity, nH < 1.0. Therefore, for a distinctive set of ligands, the extracellular domain of a nAChR surrogate suffices to accommodate cooperative interactions. X-ray crystal structures of AChBP complexes with examples of each allowed the identification of structural features in the ligands that confer differences in cooperative behavior. Both sets of molecules bind at the agonist-antagonist site, as expected from their competition with epibatidine. An analysis of AChBP quaternary structure shows that cooperative ligand binding is associated with a blooming or flare conformation, a structural change not observed with the classical, noncooperative, nicotinic ligands. Positively and negatively cooperative ligands exhibited unique features in the detailed binding determinants and poses of the complexes. Structural basis for cooperative interactions of substituted 2-aminopyrimidines with the acetylcholine binding protein.,Kaczanowska K, Harel M, Radic Z, Changeux JP, Finn MG, Taylor P Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):10749-54. doi:, 10.1073/pnas.1410992111. Epub 2014 Jul 8. PMID:25006260 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholine binding protein 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA