2w6c

ACHE IN COMPLEX WITH A BIS-(-)-NOR-MEPTAZINOL DERIVATIVE

spinqualitylabelsall models 2w6c, resolution 2.69Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2w6c is a 1 chain structure with sequence from Tetronarce californica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.69Å Ligands: BM4, NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ACES_TETCF Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions. 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 A bis-(-)-nor-meptazinol derivative in which the two meptazinol rings are linked by a nonamethylene spacer is a novel acetylcholinesterase inhibitor that inhibits both catalytic activity and Abeta peptide aggregation. The crystal structure of its complex with Torpedo californica acetylcholinesterase was determined to 2.7 A resolution. The ligand spans the active-site gorge, with one nor-meptazinol moiety bound at the "anionic" subsite of the active site, disrupting the catalytic triad by forming a hydrogen bond with His440N(epsilon2), which is hydrogen-bonded to Ser200O(gamma) in the native enzyme. The second nor-meptazinol binds at the peripheral "anionic" site at the gorge entrance. A number of GOLD models of the complex, using both native TcAChE and the protein template from the crystal structure of the bis-(-)-nor-meptazinol/TcAChE complex, bear higher similarity to the X-ray structure than a previous model obtained using the mouse enzyme structure. These findings may facilitate rational design of new meptazinol-based acetylcholinesterase inhibitors. The Crystal Structure of a Complex of Acetylcholinesterase with a Bis-(-)-nor-meptazinol Derivative Reveals Disruption of the Catalytic Triad.,Paz A, Xie Q, Greenblatt HM, Fu W, Tang Y, Silman I, Qiu Z, Sussman JL J Med Chem. 2009 Mar 27. PMID:19326912 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholinesterase 3D structures

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