3i6z

From Proteopedia

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

PDB ID 3i6z

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Structural highlights

3i6z is a 1 chain structure with sequence from Tetronarce californica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.19Å
Ligands:	,
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.

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

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^[1]

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

References

↑ 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