5ov9

Crystal structure of Acetylcholinesterase in complex with Crystal VioletCrystal structure of Acetylcholinesterase in complex with Crystal Violet

Structural highlights 5ov9 is a 2 chain structure with sequence from Mus musculus. 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: , , , , , , , , Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ACES_MOUSE Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Publication Abstract from PubMed Acetylcholinesterase (AChE) is an essential enzyme that terminates cholinergic transmission by a rapid hydrolysis of the neurotransmitter acetylcholine. AChE is an important target for treatment of various cholinergic deficiencies, including Alzheimer's disease and myasthenia gravis. In a previous high throughput screening campaign, we identified the dye crystal violet (CV) as an inhibitor of AChE. Herein, we show that CV displays a significant cooperativity for binding to AChE, and the molecular basis for this observation has been investigated by X-ray crystallography. Two monomers of CV bind to residues at the entrance of the active site gorge of the enzyme. Notably, the two CV molecules have extensive intermolecular contacts with each other and with AChE. Computational analyses show that the observed CV dimer is not stable in solution, suggesting the sequential binding of two monomers. Guided by the structural analysis, we designed a set of single site substitutions, and investigated their effect on the binding of CV. Only moderate effects on the binding and the cooperativity were observed, suggesting a robustness in the interaction between CV and AChE. Taken together, we propose that the dimeric cooperative binding is due to a rare combination of chemical and structural properties of both CV and the AChE molecule itself. An Unusual Dimeric Inhibitor of Acetylcholinesterase: Cooperative Binding of Crystal Violet.,Allgardsson A, David Andersson C, Akfur C, Worek F, Linusson A, Ekstrom F Molecules. 2017 Aug 30;22(9). pii: E1433. doi: 10.3390/molecules22091433. PMID:28867801 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholinesterase 3D structures

spinqualitylabelsall models 5ov9, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image