PDBsum entry 1zgb

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protein ligands links
Hydrolase PDB id
Protein chain
528 a.a. *
NAG ×2
Waters ×178
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Crystal structure of torpedo californica acetylcholinesteras complex with an (r)-tacrine(10)-hupyridone inhibitor.
Structure: Acetylcholinesterase. Chain: a. Synonym: ache. Ec:
Source: Torpedo californica. Pacific electric ray. Organism_taxid: 7787
Biol. unit: Dimer (from PDB file)
2.30Å     R-factor:   0.188     R-free:   0.230
Authors: H.Haviv,D.M.Wong,H.M.Greenblatt,P.R.Carlier,Y.P.Pang,I.Silma J.L.Sussman,Israel Structural Proteomics Center (Ispc)
Key ref: H.Haviv et al. (2005). Crystal packing mediates enantioselective ligand recognition at the peripheral site of acetylcholinesterase. J Am Chem Soc, 127, 11029-11036. PubMed id: 16076210 DOI: 10.1021/ja051765f
21-Apr-05     Release date:   16-Aug-05    
Go to PROCHECK summary

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

 Enzyme reactions 
   Enzyme class: E.C.  - Acetylcholinesterase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: Acetylcholine + H2O = choline + acetate
Bound ligand (Het Group name = NAG)
matches with 41.18% 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     hydrolase activity     3 terms  


DOI no: 10.1021/ja051765f J Am Chem Soc 127:11029-11036 (2005)
PubMed id: 16076210  
Crystal packing mediates enantioselective ligand recognition at the peripheral site of acetylcholinesterase.
H.Haviv, D.M.Wong, H.M.Greenblatt, P.R.Carlier, Y.P.Pang, I.Silman, J.L.Sussman.
Recently, alkylene-linked heterodimers of tacrine (1) and 5-amino-5,6,7,8-tetrahydroquinolinone (2, hupyridone) were shown to exhibit higher acetylcholinesterase (AChE) inhibition than either monomeric 1 or 2. Such inhibitors are potential drug candidates for ameliorating the cognitive decrements in early Alzheimer patients. In an attempt to understand the inhibition mechanism of one such dimer, (RS)-(+/-)-N-9-(1,2,3,4-tetrahydroacridinyl)-N'-5-[5,6,7,8-tetrahydro-2'(1'H)-quinolinonyl]-1,10-diaminodecane [(RS)-(+/-)-3] bisoxalate, the racemate was soaked in trigonal Torpedo californica AChE (TcAChE) crystals, and the X-ray structure of the resulting complex was solved to 2.30 A resolution. Its structure revealed the 1 unit bound to the "anionic" subsite of the active site, near the bottom of the active-site gorge, as seen for the 1/TcAChE complex. Interestingly, only the (R)-enantiomer of the 2 unit was seen in the peripheral "anionic" site (PAS) at the top of the gorge, and was hydrogen-bonded to the side chains of residues belonging to an adjacent, symmetry-related AChE molecule covering the gorge entrance. When the same racemate was soaked in orthorhombic crystals of TcAChE, in which the entrance to the gorge is more exposed, the crystal structure of the corresponding complex revealed no substantial enantiomeric selectivity. This observation suggests that the apparent enantiomeric selectivity of trigonal crystals of TcAChE for (R)-3 is mainly due to crystal packing, resulting in preferential binding of one enantiomeric inhibitor both to its "host" enzyme and to its neighbor in the asymmetric unit, rather than to steric constraints imposed by the geometry of the active-site gorge.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21202575 L.Zhang, D.Shi, J.Li, L.Zhang, and Y.Fan (2008).
1-Phenyl-6,7,8,9-hexa-hydro-1H,5H-cyclo-hepta-[1',2':2,3]pyrido[6,5-c]pyrazol-4-amine: a new tacrine analogue.
  Acta Crystallogr Sect E Struct Rep Online, 64, o1056.  
18033585 J.Stöckigt, and S.Panjikar (2007).
Structural biology in plant natural product biosynthesis--architecture of enzymes from monoterpenoid indole and tropane alkaloid biosynthesis.
  Nat Prod Rep, 24, 1382-1400.  
16791318 G.Pastorin, S.Marchesan, J.Hoebeke, T.Da Ros, L.Ehret-Sabatier, J.P.Briand, M.Prato, and A.Bianco (2006).
Design and activity of cationic fullerene derivatives as inhibitors of acetylcholinesterase.
  Org Biomol Chem, 4, 2556-2562.  
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