PDBsum entry 2j4f

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protein metals links
Hydrolase PDB id
Protein chain
527 a.a. *
_HG ×2
Waters ×94
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Torpedo acetylcholinesterase - hg heavy-atom derivative
Structure: Acetylcholinesterase. Chain: a. Fragment: residues 22-564. Synonym: ache. Ec:
Source: Torpedo californica. Pacific electric ray. Organism_taxid: 7787
2.8Å     R-factor:   0.204     R-free:   0.262
Authors: D.I.Kreimer,E.A.Dolginova,M.Raves,J.L.Sussman,I.Silman, L.Weiner
Key ref:
D.I.Kreimer et al. (1994). A metastable state of Torpedo californica acetylcholinesterase generated by modification with organomercurials. Biochemistry, 33, 14407-14418. PubMed id: 7981200 DOI: 10.1021/bi00252a006
30-Aug-06     Release date:   05-Sep-06    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P04058  (ACES_TORCA) -  Acetylcholinesterase
586 a.a.
527 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
+ 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: 10.1021/bi00252a006 Biochemistry 33:14407-14418 (1994)
PubMed id: 7981200  
A metastable state of Torpedo californica acetylcholinesterase generated by modification with organomercurials.
D.I.Kreimer, E.A.Dolginova, M.Raves, J.L.Sussman, I.Silman, L.Weiner.
Chemical modification of Torpedo californica acetylcholinesterase by various sulfhydryl reagents results in its conversion to one of two principal states. One of these states, viz., that produced by disulfides and alkylating agents, is stable. The second state, produced by mercury derivatives, is metastable. At room temperature, it converts spontaneously, with a half-life of ca. 1 h, to a stable state similar to that produced by the disulfides and alkylating agents. Demodification of acetylcholinesterase freshly modified by mercurials, by its exposure to reduced glutathione, causes rapid release of the bound mercurial, with concomitant recovery of most of the enzymic activity of the native enzyme. In contrast, similar demodification of acetylcholinesterase modified by disulfides yields no detectable recovery of enzymic activity. Spectroscopic measurements, employing CD, intrinsic fluorescence, and binding of 1-anilino-8-naphthalenesulfonate, show that the state produced initially by mercurials is "native-like", whereas that produced by disulfides and alkylating agents, and after prolonged incubation of the mercurial-modified enzyme, is partially unfolded and displays many of the features of the "molten globule" state. Arrhenius plots show that the quasi-native state produced by organomercurials is separated by a low (5 kcal/mol) energy barrier from the native state, whereas the partially unfolded state is separated from the quasi-native state by a high energy barrier (ca. 50 kcal/mol). Comparison of the 3D structures of native acetylcholinesterase and of a heavy-atom derivative obtained with HgAc2 suggests that the mercurial-modified enzyme may be stabilized by additional interactions of the mercury atom attached to the free thiol group of Cys231, specifically with Ser228O gamma with the main-chain nitrogen and carbonyl oxygen of the same serine residue.

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.  
17966129 A.Badiou, J.L.Brunet, and L.P.Belzunces (2007).
Existence of two membrane-bound acetylcholinesterases in the honey bee head.
  Arch Insect Biochem Physiol, 66, 122-134.  
17355286 M.F.Frasco, J.P.Colletier, M.Weik, F.Carvalho, L.Guilhermino, J.Stojan, and D.Fournier (2007).
Mechanisms of cholinesterase inhibition by inorganic mercury.
  FEBS J, 274, 1849-1861.
PDB code: 2j4c
14500892 C.B.Millard, V.L.Shnyrov, S.Newstead, I.Shin, E.Roth, I.Silman, and L.Weiner (2003).
Stabilization of a metastable state of Torpedo californica acetylcholinesterase by chemical chaperones.
  Protein Sci, 12, 2337-2347.  
12142456 I.Shin, E.Wachtel, E.Roth, C.Bon, I.Silman, and L.Weiner (2002).
Thermal denaturation of Bungarus fasciatus acetylcholinesterase: Is aggregation a driving force in protein unfolding?
  Protein Sci, 11, 2022-2032.  
11087367 D.I.Kreimer, K.P.Chai, and G.Ferro-Luzzi Ames (2000).
Nonequivalence of the nucleotide-binding subunits of an ABC transporter, the histidine permease, and conformational changes in the membrane complex.
  Biochemistry, 39, 14183-14195.  
9096309 I.Shin, D.Kreimer, I.Silman, and L.Weiner (1997).
Membrane-promoted unfolding of acetylcholinesterase: a possible mechanism for insertion into the lipid bilayer.
  Proc Natl Acad Sci U S A, 94, 2848-2852.  
  9144779 M.Peretz, L.M.Weiner, and Y.Burstein (1997).
Cysteine reactivity in Thermoanaerobacter brockii alcohol dehydrogenase.
  Protein Sci, 6, 1074-1083.  
  8771195 I.Shin, I.Silman, and L.M.Weiner (1996).
Interaction of partially unfolded forms of Torpedo acetylcholinesterase with liposomes.
  Protein Sci, 5, 42-51.  
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