2uz6 | pdb_00002uz6

AChBP-targeted a-conotoxin correlates distinct binding orientations with nAChR subtype selectivity.

spinqualitylabelsall models 2uz6, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2uz6 is a 20 chain structure with sequence from Aplysia californica and Conus textile. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.4Å Ligands: GOL, NAG, NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q8WSF8_APLCA Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Neuronal nAChRs are a diverse family of pentameric ion channels with wide distribution throughout cells of the nervous and immune systems. However, the role of specific subtypes in normal and pathological states remains poorly understood due to the lack of selective probes. Here, we used a binding assay based on acetylcholine-binding protein (AChBP), a homolog of the nicotinic acetylcholine ligand-binding domain, to discover a novel alpha-conotoxin (alpha-TxIA) in the venom of Conus textile. Alpha-TxIA bound with high affinity to AChBPs from different species and selectively targeted the alpha(3)beta(2) nAChR subtype. A co-crystal structure of Ac-AChBP with the enhanced potency analog TxIA(A10L), revealed a 20 degrees backbone tilt compared to other AChBP-conotoxin complexes. This reorientation was coordinated by a key salt bridge formed between Arg5 (TxIA) and Asp195 (Ac-AChBP). Mutagenesis studies, biochemical assays and electrophysiological recordings directly correlated the interactions observed in the co-crystal structure to binding affinity at AChBP and different nAChR subtypes. Together, these results establish a new pharmacophore for the design of novel subtype-selective ligands with therapeutic potential in nAChR-related diseases. AChBP-targeted alpha-conotoxin correlates distinct binding orientations with nAChR subtype selectivity.,Dutertre S, Ulens C, Buttner R, Fish A, van Elk R, Kendel Y, Hopping G, Alewood PF, Schroeder C, Nicke A, Smit AB, Sixma TK, Lewis RJ EMBO J. 2007 Aug 22;26(16):3858-67. Epub 2007 Jul 26. PMID:17660751 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholine binding protein 3D structures

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