2bag

3D Structure of Torpedo californica acetylcholinesterase complexed with Ganstigmine3D Structure of Torpedo californica acetylcholinesterase complexed with Ganstigmine

Structural highlights 2bag 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 2.4Å Ligands: , , , 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 Ganstigmine is an orally active, geneserine derived, carbamate-based acetylcholinesterase inhibitor developed for the treatment of Alzheimer's disease. The crystal structure of the ganstigmine conjugate with Torpedo californica acetylcholinesterase (TcAChE) has been determined at 2.40 A resolution, and a detailed structure-based analysis of the in vitro and ex vivo anti-AChE activity by ganstigmine and by new geneserine derivatives is presented. The carbamoyl moiety is covalently bound to the active-site serine, whereas the leaving group geneseroline is not retained in the catalytic pocket. The nitrogen atom of the carbamoyl moiety of ganstigmine is engaged in a key hydrogen-bonding interaction with the active site histidine (His440). This result offers an explanation for the inactivation of the catalytic triad and may account for the long duration of action of ganstigmine in vivo. The 3D structure also provides a structural framework for the design of compounds with improved binding affinity and pharmacological properties. Structural determinants of Torpedo californica acetylcholinesterase inhibition by the novel and orally active carbamate based anti-alzheimer drug ganstigmine (CHF-2819).,Bartolucci C, Siotto M, Ghidini E, Amari G, Bolzoni PT, Racchi M, Villetti G, Delcanale M, Lamba D J Med Chem. 2006 Aug 24;49(17):5051-8. PMID:16913695 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholinesterase 3D structures

spinqualitylabelsall models 2bag, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image