Structural highlights
6ezh is a 2 chain structure with sequence from Tetronarce californica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
|
| Ligands: | , |
| Related: | 1ea5, 2w75, 1eve, 6ezg |
| Activity: | Acetylcholinesterase, with EC number 3.1.1.7 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[ACES_TETCF] 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.
Publication Abstract from PubMed
Pleiotropic intervention may be a requirement for effective limitation of the progression of multifactorial diseases such as Alzheimer's Disease. One approach to such intervention is to design a single chemical entity capable of acting on two or more targets of interest, which are accordingly known as Multi-Target Directed Ligands (MTDLs). We recently described donecopride, the first MTDL able to simultaneously inhibit acetylcholinesterase and act as an agonist of the 5-HT4 receptor, which displays promising activities in vivo. Pharmacomodulation of donecopride allowed us to develop a novel series of indole derivatives possessing interesting in vitro activities toward AChE and the sigma1 receptor. The crystal structures of complexes of the most promising compounds with Torpedo californica AChE were solved in order to further understand their mode of inhibition.
Novel multitarget-directed ligands targeting acetylcholinesterase and sigma1 receptors as lead compounds for treatment of Alzheimer's disease: Synthesis, evaluation, and structural characterization of their complexes with acetylcholinesterase.,Lalut J, Santoni G, Karila D, Lecoutey C, Davis A, Nachon F, Silman I, Sussman J, Weik M, Maurice T, Dallemagne P, Rochais C Eur J Med Chem. 2018 Nov 8;162:234-248. doi: 10.1016/j.ejmech.2018.10.064. PMID:30447434[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lalut J, Santoni G, Karila D, Lecoutey C, Davis A, Nachon F, Silman I, Sussman J, Weik M, Maurice T, Dallemagne P, Rochais C. Novel multitarget-directed ligands targeting acetylcholinesterase and sigma1 receptors as lead compounds for treatment of Alzheimer's disease: Synthesis, evaluation, and structural characterization of their complexes with acetylcholinesterase. Eur J Med Chem. 2018 Nov 8;162:234-248. doi: 10.1016/j.ejmech.2018.10.064. PMID:30447434 doi:http://dx.doi.org/10.1016/j.ejmech.2018.10.064
