5bwc | pdb_00005bwc

ACETYLCHOLINESTERASE (E.C. 3.1.1.7) FROM TORPEDO CALIFORNICA IN COMPLEX WITH THE BIS-PYRIDINIUM OXIME ORTHO-7

spinqualitylabelsall models 5bwc, resolution 2.45Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 5bwc 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 2.45Å Ligands: HBP, 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. Publication Abstract from PubMed As part of ongoing efforts to design improved nerve agent antidotes, two X-ray crystal structures of Torpedo californica acetylcholinesterase (TcAChE) bound to the bis-pyridinium oxime, Ortho-7, or its experimental bis-imidazolium analogue, 2BIM-7, were determined. Bis-oximes contain two oxime groups connected by a hydrophobic linker. One oxime group of Ortho-7 binds at the entrance to the active-site gorge near Trp279, and the second binds at the bottom near Trp84 and Phe330. In the Ortho-7-TcAChE complex the oxime at the bottom of the gorge was directed towards the nucleophilic Ser200. In contrast, the oxime group of 2BIM-7 was rotated away from Ser200 and the oxime at the entrance induced a significant conformational change in the peripheral anionic site (PAS) residue Trp279. The conformational change alters the surface of the PAS and positions the imidazolium oxime of 2BIM-7 further from Ser200. The relatively weaker binding and poorer reactivation of VX-inhibited, tabun-inhibited or sarin-inhibited human acetylcholinesterase by 2BIM-7 compared with Ortho-7 may in part be owing to the unproductively bound states caught in crystallo. Overall, the reactivation efficiency of 2BIM-7 was comparable to that of 2-pyridine aldoxime methyl chloride (2-PAM), but unlike 2-PAM the bis-imidazolium oxime lacks a fixed charge, which may affect its membrane permeability. A conformational change in the peripheral anionic site of Torpedo californica acetylcholinesterase induced by a bis-imidazolium oxime.,Legler PM, Soojhawon I, Millard CB Acta Crystallogr D Biol Crystallogr. 2015 Sep 1;71(Pt 9):1788-98. doi:, 10.1107/S1399004715011281. Epub 2015 Aug 25. PMID:26327369 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholinesterase 3D structures

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