Acetylcholinesterase with acetylcholine

spinqualitylabelsall models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D ACETYLCHOLINESTERASE (E.C. 3.1.1.7) FROM TORPEDO CALIFORNICA (see also AChE inhibitors and substrates) Publication Abstract from PubMed (-)-Huperzine A (HupA) is found in an extract from a club moss that has been used for centuries in Chinese folk medicine. Its action has been attributed to its ability to strongly inhibit acetylcholinesterase (AChE). The crystal structure of the complex of AChE with optically pure HupA at 2.5 A resolution shows an unexpected orientation for the inhibitor with surprisingly few strong direct interactions with protein residues to explain its high affinity. This structure is compared to the native structure of AChE devoid of any inhibitor as determined to the same resolution. An analysis of the affinities of structural analogues of HupA, correlated with their interactions with the protein, shows the importance of individual hydrophobic interactions between HupA and aromatic residues in the active-site gorge of AChE. Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A., Raves ML, Harel M, Pang YP, Silman I, Kozikowski AP, Sussman JL, Nat Struct Biol. 1997 Jan;4(1):57-63. PMID:8989325 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. Overview Solution of the three-dimensional (3D) structure of Torpedo californica acetylcholinesterase (TcAChE) in 1991 (Sussman et al. & Silman (1991)) opened up new horizons in research on an enzyme that had already been the subject of intensive investigation. The unanticipated structure of this extremely rapid enzyme, in which the active site was found to be buried at the bottom of a deep and narrow gorge, lined by 14 aromatic residues (colored darkmagenta), led to a revision of the views then held concerning substrate traffic, recognition, and hydrolysis (Botti et al. Sussman & Silman (1999)). This led to a series of theoretical and experimental studies, which took advantage of recent advances in theoretical techniques for treatment of proteins, such as molecular dynamics and electrostatics and to site-directed mutagenesis, utilizing suitable expression systems. Acetylcholinesterase hydrolysizes the neurotransmitter acetylcholine (ACh), producing choline and an acetate group. ACh directly binds Ser200 (via its nucleophilic Oγ atom) within the catalytic triad (Ser200, His440, and Glu327). The residues Trp84 and Phe330 are also important in the ligand recognition. After this binding acetylcholinesterase hydrolysizes ACh. About this Structure 2ACE is a Single protein structure of sequence from Torpedo californica with ACH as ligand. This structure superseeds the now removed PDB entry 1ACE. Active as Acetylcholinesterase, with EC number 3.1.1.7 Structure known Active Site: CAT. Full crystallographic information is available from OCA. Additional Resources For additional information, see: Alzheimer's Disease

Reference

Structure of acetylcholinesterase complexed with the nootropic alkaloid, (-)-huperzine A., Raves ML, Harel M, Pang YP, Silman I, Kozikowski AP, Sussman JL, Nat Struct Biol. 1997 Jan;4(1):57-63. PMID:8989325

• Created with the participation of Joel L. Sussman, Jaime Prilusky, David Canner.

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