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3i6m

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3i6m, resolution 2.26Å ()
Sites: , , and
Ligands: ,
Activity: Acetylcholinesterase, with EC number 3.1.1.7
Related: 1w4l, 1w6r, 1qti, 1w76, 1dx6, 3i6z
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Contents

3D Structure of Torpedo californica acetylcholinesterase complexed with N-piperidinopropyl-galanthamine

Publication Abstract from PubMed

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).

Probing Torpedo californica Acetylcholinesterase Catalytic Gorge with Two Novel Bis-functional Galanthamine Derivatives., Bartolucci C, Haller LA, Jordis U, Fels G, Lamba D, J Med Chem. 2009 Dec 21. PMID:20025280

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

About this Structure

3i6m is a 1 chain structure of Acetylcholinesterase with sequence from Torpedo californica. Full crystallographic information is available from OCA.

See Also

Reference

  • Bartolucci C, Haller LA, Jordis U, Fels G, Lamba D. Probing Torpedo californica Acetylcholinesterase Catalytic Gorge with Two Novel Bis-functional Galanthamine Derivatives. J Med Chem. 2009 Dec 21. PMID:20025280 doi:10.1021/jm901296p
  • Greenblatt HM, Guillou C, Guenard D, Argaman A, Botti S, Badet B, Thal C, Silman I, Sussman JL. The complex of a bivalent derivative of galanthamine with torpedo acetylcholinesterase displays drastic deformation of the active-site gorge: implications for structure-based drug design. J Am Chem Soc. 2004 Dec 1;126(47):15405-11. PMID:15563167 doi:10.1021/ja0466154
  • Greenblatt HM, Kryger G, Lewis T, Silman I, Sussman JL. Structure of acetylcholinesterase complexed with (-)-galanthamine at 2.3 A resolution. FEBS Lett. 1999 Dec 17;463(3):321-6. PMID:10606746
  • Bartolucci C, Perola E, Pilger C, Fels G, Lamba D. Three-dimensional structure of a complex of galanthamine (Nivalin) with acetylcholinesterase from Torpedo californica: implications for the design of new anti-Alzheimer drugs. Proteins. 2001 Feb 1;42(2):182-91. PMID:11119642
  • Pilger C, Bartolucci C, Lamba D, Tropsha A, Fels G. Accurate prediction of the bound conformation of galanthamine in the active site of Torpedo californica acetylcholinesterase using molecular docking. J Mol Graph Model. 2001;19(3-4):288-96, 374-8. PMID:11449566
  • Luttmann E, Linnemann E, Fels G. Galanthamine as bis-functional ligand for the acetylcholinesterase. J Mol Model. 2002 Jun;8(6):208-16. PMID:12140604 doi:10.1007/s00894-002-0086-9
  • Alisaraie L, Haller LA, Fels G. A QXP-based multistep docking procedure for accurate prediction of protein-ligand complexes. J Chem Inf Model. 2006 May-Jun;46(3):1174-87. PMID:16711737 doi:10.1021/ci050343m

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