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PDBsum entry 3i6z

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protein ligands links
Hydrolase PDB id
3i6z
Jmol
Contents
Protein chain
532 a.a. *
Ligands
NAG
NAG-NAG
G6X
Waters ×374
* Residue conservation analysis
PDB id:
3i6z
Name: Hydrolase
Title: 3d structure of torpedo californica acetylcholinesterase complexed with n-saccharinohexyl-galanthamine
Structure: Acetylcholinesterase. Chain: a. Fragment: unp residues 23-556. Synonym: ache. Ec: 3.1.1.7
Source: Torpedo californica. Pacific electric ray. Organism_taxid: 7787
Resolution:
2.19Å     R-factor:   0.183     R-free:   0.212
Authors: D.Lamba,C.Bartolucci
Key ref: C.Bartolucci et al. (2010). Probing Torpedo californica acetylcholinesterase catalytic gorge with two novel bis-functional galanthamine derivatives. J Med Chem, 53, 745-751. PubMed id: 20025280
Date:
07-Jul-09     Release date:   12-Jan-10    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P04058  (ACES_TORCA) -  Acetylcholinesterase
Seq:
Struc:
 
Seq:
Struc:
586 a.a.
532 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.1.1.7  - Acetylcholinesterase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetylcholine + H2O = choline + acetate
Acetylcholine
Bound ligand (Het Group name = NAG)
matches with 41.00% similarity
+ H(2)O
= choline
+ acetate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     synapse   5 terms 
  Biological process     neurotransmitter catabolic process   2 terms 
  Biochemical function     carboxylic ester hydrolase activity     4 terms  

 

 
    reference    
 
 
J Med Chem 53:745-751 (2010)
PubMed id: 20025280  
 
 
Probing Torpedo californica acetylcholinesterase catalytic gorge with two novel bis-functional galanthamine derivatives.
C.Bartolucci, L.A.Haller, U.Jordis, G.Fels, D.Lamba.
 
  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).