3I6M
3D Structure of Torpedo californica acetylcholinesterase complexed with N-piperidinopropyl-galanthamine
Summary for 3I6M
| Entry DOI | 10.2210/pdb3i6m/pdb |
| Related | 1DX6 1QTI 1W4L 1W6R 1W76 3I6Z |
| 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, ... (5 entities in total) |
| Functional Keywords | serine hydrolase, cholinesterase, neurotransmitter degradation, alzheimer's disease, bis-functional galanthamine derivative, alternative splicing, cell junction, cell membrane, disulfide bond, glycoprotein, gpi-anchor, hydrolase, lipoprotein, membrane, serine esterase, synapse |
| Biological source | Torpedo californica (Pacific electric ray) |
| Cellular location | Isoform H: Cell membrane; Lipid-anchor, GPI- anchor. Isoform T: Cell membrane; Peripheral membrane protein: P04058 |
| Total number of polymer chains | 1 |
| Total formula weight | 61491.36 |
| Authors | Lamba, D.,Bartolucci, C. (deposition date: 2009-07-07, release date: 2010-01-12, Last modification date: 2023-09-06) |
| Primary citation | Bartolucci, C.,Haller, L.A.,Jordis, U.,Fels, G.,Lamba, D. Probing Torpedo californica acetylcholinesterase catalytic gorge with two novel bis-functional galanthamine derivatives. J.Med.Chem., 53:745-751, 2010 Cited by PubMed Abstract: N-Piperidinopropyl-galanthamine (2) and N-saccharinohexyl-galanthamine (3) were used to investigate interaction sites along the active site gorge of Torpedo californica actylcholinesterase (TcAChE). The crystal structure of TcAChE-2 solved at 2.3 A showed that the N-piperidinopropyl group in 2 is not stretched along the gorge but is folded over the galanthamine moiety. This result was unexpected because the three carbon alkyl chain is just long enough for the bulky piperidine group to be placed above the bottleneck (Tyr121, Phe330) midway down the gorge. The crystal structure of TcAChE-3 at 2.2 A confirmed that a dual interaction with the sites at the bottom, and at the entrance of the gorge, enhances inhibitory activity: a chain of six carbon atoms has, in this class of derivatives, the correct length for optimal interactions with the peripheral anionic site (PAS). PubMed: 20025280DOI: 10.1021/jm901296p PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.26 Å) |
Structure validation
Download full validation report
