1gqs | pdb_00001gqs

ACETYLCHOLINESTERASE (E.C. 3.1.1.7) COMPLEXED WITH NAP

spinqualitylabelsall models 1gqs, resolution 3.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1gqs is a 1 chain structure with sequence from Torpedo californica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAG, SAF Related: 1acj, 1acl, 1amn, 1ax9, 1cfj, 1dx6, 1e3q, 1e66, 1ea5, 1eea, 1eve, 1fss, 1gpk, 1gpn, 1hbj, 1oce, 1qid, 1qie, 1qif, 1qig, 1qih, 1qii, 1qij, 1qik, 1qim, 1qti, 1som, 1vot, 1vxo, 1vxr, 2ace, 2ack, 2dfp, 3ace, 4ace, 1gqr Activity: Acetylcholinesterase, with EC number 3.1.1.7 Resources: FirstGlance, OCA, RCSB, PDBsum 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 Rivastigmine, a carbamate inhibitor of acetylcholinesterase, is already in use for treatment of Alzheimer's disease under the trade name of Exelon. Rivastigmine carbamylates Torpedo californica acetylcholinesterase very slowly (k(i) = 2.0 M(-1) min(-1)), whereas the bimolecular rate constant for inhibition of human acetylcholinesterase is >1600-fold higher (k(i) = 3300 M(-1) min(-1)). For human butyrylcholinesterase and for Drosophila melanogaster acetylcholinesterase, carbamylation is even more rapid (k(i) = 9 x 10(4) and 5 x 10(5) M(-1) min(-1), respectively). Spontaneous reactivation of all four conjugates is very slow, with <10% reactivation being observed for the Torpedo enzyme after 48 h. The crystal structure of the conjugate of rivastigmine with Torpedo acetylcholinesterase was determined to 2.2 A resolution. It revealed that the carbamyl moiety is covalently linked to the active-site serine, with the leaving group, (-)-S-3-[1-(dimethylamino)ethyl]phenol, being retained in the "anionic" site. A significant movement of the active-site histidine (H440) away from its normal hydrogen-bonded partner, E327, was observed, resulting in disruption of the catalytic triad. This movement may provide an explanation for the unusually slow kinetics of reactivation. Kinetic and structural studies on the interaction of cholinesterases with the anti-Alzheimer drug rivastigmine.,Bar-On P, Millard CB, Harel M, Dvir H, Enz A, Sussman JL, Silman I Biochemistry. 2002 Mar 19;41(11):3555-64. PMID:11888271 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also AChE inhibitors and substrates AChE inhibitors and substrates (Part III) Acetylcholinesterase

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