4b81 | pdb_00004b81

Mus musculus Acetylcholinesterase in complex with 1-(4-Chloro-phenyl)- N-(2-diethylamino-ethyl)-methanesulfonamide

spinqualitylabelsall models 4b81, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4b81 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. Ligands: NAG, P6G, PEG, SO4, ZN4 Related: 1c2b, 1c2o, 1j06, 1j07, 1ku6, 1maa, 1mah, 1n5m, 1n5r, 1q83, 1q84, 2c0p, 2c0q, 2h9y, 2ha0, 2ha2, 2ha3, 2ha4, 2ha5, 2ha6, 2ha7, 2jey, 2jez, 2jf0, 2jge, 2jgf, 2jgg, 2jgh, 2jgi, 2jgj, 2jgk, 2jgl, 2jgm, 2whp, 2whq, 2whr, 2wls, 2wu3, 2wu4, 2xud, 2xuf, 2xug, 2xuh, 2xui, 2xuj, 2xuk, 2xuo, 2xup, 2xuq, 4a16, 4a23, 4ara, 4arb, 4b7z, 4b80, 4b82, 4b83, 4b84, 4b85 Activity: Acetylcholinesterase, with EC number 3.1.1.7 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The molecular interactions between the enzyme acetylcholinesterase (AChE) and two compound classes consisting of N-[2-(diethylamino)-ethyl]-benzenesulfonamides and N-[2-(diethylamino)-ethyl]-benzenemethanesulfonamides have been investigated using organic synthesis, enzymatic assays, X-ray crystallography, and thermodynamic profiling. The inhibitors' aromatic properties were varied to establish structure-activity relationships (SAR) between the inhibitors and the peripheral anionic site (PAS) of AChE. The two structurally similar compound classes proved to have distinctly divergent SARs in terms of their inhibition capacity of AChE. Eight X-ray structures revealed that the two sets have different conformations in PAS. Furthermore, thermodynamic profiles of the binding between compounds and AChE revealed class-dependent differences of the entropy/enthalpy contributions to the free energy of binding. Further development of the entropy-favored compound class resulted in the synthesis of the most potent inhibitor, and an extension beyond the established SARs. The divergent SARs will be utilized to develop reversible inhibitors of AChE into reactivators of nerve agent inhibited AChE. Divergent Structure-Activity Relationships of Structurally Similar Acetylcholinesterase Inhibitors.,Andersson CD, Forsgren N, Akfur C, Allgardsson A, Berg L, Engdahl C, Qian W, Ekstrom FJ, Linusson A J Med Chem. 2013 Aug 28. PMID:23984975 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Acetylcholinesterase

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