1UT6
Structure of acetylcholinesterase (E.C. 3.1.1.7) complexed with N-9-(1',2',3',4'-Tetrahydroacridinyl)-1,8- diaminooctane at 2.4 angstroms resolution.
Summary for 1UT6
| Entry DOI | 10.2210/pdb1ut6/pdb |
| Related | 1ACJ 1ACL 1AMN 1AX9 1CFJ 1DX6 1E3Q 1E66 1EA5 1EEA 1EVE 1FSS 1GPK 1GPN 1GQR 1GQS 1H22 1H23 1HBJ 1JJB 1OCE 1ODC 1QID 1QIE 1QIF 1QIG 1QIH 1QII 1QIJ 1QIK 1QIM 1QTI 1SOM 1VOT 1VXO 1VXR 2ACE 2ACK 2DFP 3ACE 4ACE |
| Descriptor | ACETYLCHOLINESTERASE, 2-acetamido-2-deoxy-beta-D-glucopyranose, N-9-(1',2',3',4'-TETRAHYDROACRIDINYL)-1,8-DIAMINOOCTANE, ... (4 entities in total) |
| Functional Keywords | hydrolase, serine hydrolase, acetylcholinesterase, neurotransmitter cleavage, alzheimer's disease, bivalent ligand, dual-site binding, inhibitor, tacrine, amine, heterodimer, serine esterase synapse, membrane, nerve, muscle, gpi-anchor neurotransmitter degradation, glycoprotein |
| Biological source | TORPEDO CALIFORNICA (PACIFIC ELECTRIC RAY) |
| Total number of polymer chains | 1 |
| Total formula weight | 61562.44 |
| Authors | Brumshtein, B.,Wong, D.M.,Greenblatt, H.M.,Carlier, P.R.,Pang, Y.-P.,Silman, I.,Sussman, J.L. (deposition date: 2003-12-04, release date: 2005-04-21, Last modification date: 2024-10-16) |
| Primary citation | Rydberg, E.H.,Brumshtein, B.,Greenblatt, H.M.,Wong, D.M.,Shaya, D.,Williams, L.D.,Carlier, P.R.,Pang, Y.-P.,Silman, I.,Sussman, J.L. Complexes of Alkylene-Linked Tacrine Dimers with Torpedo Californica Acetylcholinesterase: Binding of Bis(5)-Tacrine Produces a Dramatic Rearrangement in the Active-Site Gorge. J.Med.Chem., 49:5491-, 2006 Cited by PubMed Abstract: The X-ray crystal structures were solved for complexes with Torpedo californica acetylcholinesterase of two bivalent tacrine derivative compounds in which the two tacrine rings were separated by 5- and 7-carbon spacers. The derivative with the 7-carbon spacer spans the length of the active-site gorge, making sandwich interactions with aromatic residues both in the catalytic anionic site (Trp84 and Phe330) at the bottom of the gorge and at the peripheral anionic site near its mouth (Tyr70 and Trp279). The derivative with the 5-carbon spacer interacts in a similar manner at the bottom of the gorge, but the shorter tether precludes a sandwich interaction at the peripheral anionic site. Although the upper tacrine group does interact with Trp279, it displaces the phenyl residue of Phe331, thus causing a major rearrangement in the Trp279-Ser291 loop. The ability of this inhibitor to induce large-scale structural changes in the active-site gorge of acetylcholinesterase has significant implications for structure-based drug design because such conformational changes in the target enzyme are difficult to predict and to model. PubMed: 16942022DOI: 10.1021/JM060164B PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.4 Å) |
Structure validation
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