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PDBsum entry 1e3q

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Hydrolase PDB id
1e3q
Jmol
Contents
Protein chain
533 a.a. *
Ligands
EBW
SO4
NAG ×3
Waters ×128
* Residue conservation analysis
PDB id:
1e3q
Name: Hydrolase
Title: Torpedo californica acetylcholinesterase complexed with bw284c51
Structure: Acetylcholinesterase. Chain: a. Ec: 3.1.1.7
Source: Torpedo californica. Pacific electric ray. Organism_taxid: 7787. Organ: electric organ. Tissue: electroplaque
Resolution:
2.85Å     R-factor:   0.190     R-free:   0.234
Authors: C.E.Felder,M.Harel,I.Silman,J.L.Sussman
Key ref:
C.E.Felder et al. (2002). Structure of a complex of the potent and specific inhibitor BW284C51 with Torpedo californica acetylcholinesterase. Acta Crystallogr D Biol Crystallogr, 58, 1765-1771. PubMed id: 12351819 DOI: 10.1107/S0907444902011642
Date:
21-Jun-00     Release date:   03-Jul-00    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P04058  (ACES_TORCA) -  Acetylcholinesterase
Seq:
Struc:
 
Seq:
Struc:
586 a.a.
533 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 41.18% 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     carboxylic ester hydrolase activity     4 terms  

 

 
    reference    
 
 
DOI no: 10.1107/S0907444902011642 Acta Crystallogr D Biol Crystallogr 58:1765-1771 (2002)
PubMed id: 12351819  
 
 
Structure of a complex of the potent and specific inhibitor BW284C51 with Torpedo californica acetylcholinesterase.
C.E.Felder, M.Harel, I.Silman, J.L.Sussman.
 
  ABSTRACT  
 
The X-ray crystal structure of Torpedo californica acetylcholinesterase (TcAChE) complexed with BW284C51 is described and compared with the complexes of two other active-site gorge-spanning inhibitors, decamethonium and E2020. The inhibitor was soaked into TcAChE crystals in the trigonal space group P3(1)21, yielding a complex which diffracted to 2.85 A resolution. The structure was refined to an R factor of 19.0% and an R(free) of 23.4%; the final model contains the protein, inhibitor, 132 water molecules and three carbohydrate moieties. BW284C51 binds similarly to decamethonium and E2020, with its two phenyl and quaternary amino end-groups complexed to Trp84 in the catalytic site and to Trp279 in the peripheral binding site, and its central carbonyl group hydrogen bonded very weakly to Tyr121. Possible reasons for decamethonium's weaker binding are considered. The relative strength of binding of bisquaternary inhibitors to acetylcholinesterase and the effect of several mutations of the enzyme are discussed in the context of the respective X-ray structures of their complexes with the enzyme.
 
  Selected figure(s)  
 
Figure 5.
Figure 5 Schematic diagrams using LIGPLOT (Wallace et al., 1995[Wallace, A. C., Laskowski, R. A. & Thornton, J. M. (1995). Protein Eng. 8, 127-134.]), of the closest atom-atom contacts (<3.65 Å) made by (a) BW, (b) DECA and (c) E2020 with adjacent residues (excluding waters) inside the active-site gorge of TcAChE. The differences in the contacts between the three inhibitors are related to the alternate routes that they trace along the gorge and to differences in their flexibility and bulkiness.
Figure 6.
Figure 6 Stereoview of a superposition of BW, DECA and E2020 within the active-site gorge of TcAChE. The BW itself and key amino-acid residues are displayed in black, DECA and the corresponding amino-acid residues are displayed in red and E2020 and the corresponding amino-acid residues are displayed in green.
 
  The above figures are reprinted by permission from the IUCr: Acta Crystallogr D Biol Crystallogr (2002, 58, 1765-1771) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21155827 L.Weiner, E.Roth, and I.Silman (2011).
Targeted Oxidation of Torpedo californica Acetylcholinesterase by Singlet Oxygen.
  Photochem Photobiol, 87, 308-316.  
20824823 L.S.Xiao, W.Dou, Y.Li, and J.J.Wang (2010).
Comparative studies of acetylcholinesterase purified from three field populations of Liposcelis entomophila (enderlein) (psocoptera: liposcelididae).
  Arch Insect Biochem Physiol, 75, 158-173.  
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.  
16763558 J.P.Colletier, D.Fournier, H.M.Greenblatt, J.Stojan, J.L.Sussman, G.Zaccai, I.Silman, and M.Weik (2006).
Structural insights into substrate traffic and inhibition in acetylcholinesterase.
  EMBO J, 25, 2746-2756.
PDB codes: 2c4h 2c58 2c5f 2c5g
16892628 K.B.Temeyer, J.H.Pruett, P.M.Untalan, and A.C.Chen (2006).
Baculovirus expression of BmAChE3, a cDNA encoding an acetylcholinesterase of Boophilus microplus (Acari: Ixodidae).
  J Med Entomol, 43, 707-712.  
16404617 Q.Xie, Y.Tang, W.Li, X.H.Wang, and Z.B.Qiu (2006).
Investigation of the binding mode of (-)-meptazinol and bis-meptazinol derivatives on acetylcholinesterase using a molecular docking method.
  J Mol Model, 12, 390-397.  
16837465 Y.Bourne, Z.Radic, G.Sulzenbacher, E.Kim, P.Taylor, and P.Marchot (2006).
Substrate and product trafficking through the active center gorge of acetylcholinesterase analyzed by crystallography and equilibrium binding.
  J Biol Chem, 281, 29256-29267.
PDB codes: 2h9y 2ha0 2ha2 2ha3 2ha4 2ha5 2ha6 2ha7
14612446 A.Schiefner, J.Breed, L.Bösser, S.Kneip, J.Gade, G.Holtmann, K.Diederichs, W.Welte, and E.Bremer (2004).
Cation-pi interactions as determinants for binding of the compatible solutes glycine betaine and proline betaine by the periplasmic ligand-binding protein ProX from Escherichia coli.
  J Biol Chem, 279, 5588-5596.
PDB codes: 1r9l 1r9q
12505979 Y.Bourne, P.Taylor, Z.Radić, and P.Marchot (2003).
Structural insights into ligand interactions at the acetylcholinesterase peripheral anionic site.
  EMBO J, 22, 1.
PDB codes: 1j06 1j07 1ku6 1n5m 1n5r
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.