1HBJ
X-ray Crystal structure of complex between Torpedo californica AChE and a reversible inhibitor, 4-Amino-5-fluoro-2-methyl-3-(3-trifluoroacetylbenzylthiomethyl)quinoline
Summary for 1HBJ
| Entry DOI | 10.2210/pdb1hbj/pdb |
| Related | 1ACJ 1ACL 1AMN 1AX9 1CFJ 1DX6 1E3Q 1E66 1EA5 1EEA 1EVE 1FSS 1OCE 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-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total) |
| Functional Keywords | hydrolase, serine hydrolase, cholinesterase, insecticide |
| Biological source | TORPEDO CALIFORNICA (PACIFIC ELECTRIC RAY) |
| Total number of polymer chains | 1 |
| Total formula weight | 62786.59 |
| Authors | Greenblatt, H.M.,Kryger, G.,Lewis, T.L.,Doucet, C.,Viner, R.,Silman, I.,Sussman, J.L. (deposition date: 2001-04-16, release date: 2001-09-25, Last modification date: 2024-10-23) |
| Primary citation | Doucet-Personeni, C.,Bentley, P.D.,Fletcher, R.J.,Kinkaid, A.,Kryger, G.,Pirard, B.,Taylor, A.,Taylor, R.,Taylor, J.,Viner, R.,Silman, I.,Sussman, J.L.,Greenblatt, H.M.,Lewis, T.L. A Structure-Based Design Approach to the Development of Novel, Reversible Ache Inhibitors J.Med.Chem., 44:3203-, 2001 Cited by PubMed Abstract: Chimeras of tacrine and m-(N,N,N-Trimethylammonio)trifluoroacetophenone (1) were designed as novel, reversible inhibitors of acetylcholinesterase. On the basis of the X-ray structure of the apoenzyme, a molecular modeling study determined the favored attachment positions on the 4-aminoquinoline ring (position 3 and the 4-amino nitrogen) and the favored lengths of a polymethylene link between the two moieties (respectively 5-6 and 4-5 sp(3) atoms). Seven compounds matching these criteria were synthesized, and their inhibitory potencies were determined to be in the low nanomolar range. Activity data for close analogues lacking some of the postulated key features showed that our predictions were correct. In addition, a subsequent crystal structure of acetylcholinesterase complexed with the most active compound 27 was in good agreement with our model. The design strategy is therefore validated and can now be developed further. PubMed: 11563919DOI: 10.1021/JM010826R PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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