| Structural highlights
1hbj 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: | , , , |
| 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 |
| Activity: | Acetylcholinesterase, with EC number 3.1.1.7 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ACES_TORCA] Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. May be involved in cell-cell interactions.
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
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.
A structure-based design approach to the development of novel, reversible AChE inhibitors.,Doucet-Personeni C, Bentley PD, Fletcher RJ, Kinkaid A, Kryger G, Pirard B, Taylor A, Taylor R, Taylor J, Viner R, Silman I, Sussman JL, Greenblatt HM, Lewis T J Med Chem. 2001 Sep 27;44(20):3203-15. PMID:11563919[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Doucet-Personeni C, Bentley PD, Fletcher RJ, Kinkaid A, Kryger G, Pirard B, Taylor A, Taylor R, Taylor J, Viner R, Silman I, Sussman JL, Greenblatt HM, Lewis T. A structure-based design approach to the development of novel, reversible AChE inhibitors. J Med Chem. 2001 Sep 27;44(20):3203-15. PMID:11563919
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