PDBsum entry 1jjb

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protein ligands links
Hydrolase PDB id
Protein chain
532 a.a. *
NAG ×2
Waters ×623
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: A neutral molecule in cation-binding site: specific binding to acetylcholinesterase from torpedo californica
Structure: Acetylcholinesterase. Chain: a. Ec:
Source: Torpedo californica. Pacific electric ray. Organism_taxid: 7787. Strain: pacific electric ray. Other_details: electric organ
2.30Å     R-factor:   0.178     R-free:   0.224
Authors: G.Koellner,T.Steiner,C.B.Millard,I.Silman,J.L.Sussman
Key ref:
G.Koellner et al. (2002). A neutral molecule in a cation-binding site: specific binding of a PEG-SH to acetylcholinesterase from Torpedo californica. J Mol Biol, 320, 721-725. PubMed id: 12095250 DOI: 10.1016/S0022-2836(02)00475-8
04-Jul-01     Release date:   17-Jul-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P04058  (ACES_TORCA) -  Acetylcholinesterase
586 a.a.
532 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     carboxylic ester hydrolase activity     4 terms  


DOI no: 10.1016/S0022-2836(02)00475-8 J Mol Biol 320:721-725 (2002)
PubMed id: 12095250  
A neutral molecule in a cation-binding site: specific binding of a PEG-SH to acetylcholinesterase from Torpedo californica.
G.Koellner, T.Steiner, C.B.Millard, I.Silman, J.L.Sussman.
The crystal structure of acetylcholinesterase from Torpedo californica complexed with the uncharged inhibitor, PEG-SH-350 (containing mainly heptameric polyethylene glycol with a terminal thiol group) is determined at 2.3 A resolution. This is an untypical acetylcholinesterase inhibitor, since it lacks the cationic moiety typical of the substrate (acetylcholine). In the crystal structure, the elongated ligand extends along the whole of the deep and narrow active-site gorge, with the terminal thiol group bound near the bottom, close to the catalytic site. Unexpectedly, the cation-binding site (formed by the faces of aromatic side-chains) is occupied by CH(2) groups of the inhibitor, which are engaged in C-H...pi interactions that structurally mimic the cation-pi interactions made by the choline moiety of acetylcholine. In addition, the PEG-SH molecule makes numerous other weak but specific interactions of the C-H...O and C-H...pi types.
  Selected figure(s)  
Figure 1.
Figure 1. The active-site gorge of TcAChE filled with one heptamer PEG-SH molecule and 17 water molecules; some water molecules outside the gorge are also drawn/=.
Figure 3.
Figure 3. A representation of the specific intermolecular interactions formed by the PEG-SH molecule. The glycol units O7-O10 and O13-O16 are in trans conformation, and the others are in ±gauche. Of the 17 water molecules in the active-site gorge, only those that are in direct contact with PEG-SH, and those that form a link to the catalytic Ser200 are drawn. Some relevant intermolecular distances: S three dots, centered Glu199O epsilon 1=3.67 Å; S three dots, centered W1380=3.52 Å; all water-O distances <3.2 Å; C3 three dots, centered p(6-ring,midp.)Trp84=3.86 Å; C5 three dots, centered p(5-ring,midp.)Trp84=3.75 Å; C5 three dots, centered p(midp.)Phe330=3.97 Å; C14 three dots, centered p(6-ring,midp.)Trp279=3.96 Å; C17 three dots, centered p(5-ring,midp.)Trp279=3.92 Å; C12 three dots, centered OyTyr121=3.50 Å; O22 three dots, centered C^ epsilon 1Tyr70=3.80 Å; all C three dots, centered O[W] distances <3.8 Å.
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 320, 721-725) copyright 2002.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
18790485 B.Maestro, I.Velasco, I.Castillejo, M.Arévalo-Rodríguez, A.Cebolla, and J.M.Sanz (2008).
Affinity partitioning of proteins tagged with choline-binding modules in aqueous two-phase systems.
  J Chromatogr A, 1208, 189-196.  
17985237 M.A.Kamal, P.Klein, W.Luo, Y.Li, H.W.Holloway, D.Tweedie, and N.H.Greig (2008).
Kinetics of human serum butyrylcholinesterase inhibition by a novel experimental Alzheimer therapeutic, dihydrobenzodioxepine cymserine.
  Neurochem Res, 33, 745-753.  
18180869 S.K.Panigrahi (2008).
Strong and weak hydrogen bonds in protein-ligand complexes of kinases: a comparative study.
  Amino Acids, 34, 617-633.  
18502801 Y.Xu, J.P.Colletier, M.Weik, H.Jiang, J.Moult, I.Silman, and J.L.Sussman (2008).
Flexibility of aromatic residues in the active-site gorge of acetylcholinesterase: X-ray versus molecular dynamics.
  Biophys J, 95, 2500-2511.  
16570913 W.Luo, Q.S.Yu, S.S.Kulkarni, D.A.Parrish, H.W.Holloway, D.Tweedie, A.Shafferman, D.K.Lahiri, A.Brossi, and N.H.Greig (2006).
Inhibition of human acetyl- and butyrylcholinesterase by novel carbamates of (-)- and (+)-tetrahydrofurobenzofuran and methanobenzodioxepine.
  J Med Chem, 49, 2174-2185.  
16805960 Y.Ren, P.Houghton, and R.C.Hider (2006).
Relevant activities of extracts and constituents of animals used in traditional Chinese medicine for central nervous system effects associated with Alzheimer's disease.
  J Pharm Pharmacol, 58, 989-996.  
16183292 M.I.Rodríguez-Franco, M.I.Fernández-Bachiller, C.Pérez, A.Castro, and A.Martínez (2005).
Design and synthesis of N-benzylpiperidine-purine derivatives as new dual inhibitors of acetyl- and butyrylcholinesterase.
  Bioorg Med Chem, 13, 6795-6802.  
16113998 Y.Umezawa, and M.Nishio (2005).
CH/pi hydrogen bonds as evidenced in the substrate specificity of acetylcholine esterase.
  Biopolymers, 79, 248-258.  
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.