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PDBsum entry 2wg1

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protein ligands links
Hydrolase PDB id
2wg1
Jmol
Contents
Protein chain
532 a.a. *
Ligands
NAG
NAG-FUC
_GB
FP1
MES ×4
PG4 ×4
PGE ×3
PEG ×5
Waters ×555
* Residue conservation analysis
PDB id:
2wg1
Name: Hydrolase
Title: Ternary complex of the aged conjugate of torpedo californica aceylcholinesterase with soman and 2-pam
Structure: Acetylcholinesterase. Chain: a. Fragment: residues 22-558. Synonym: ache. Ec: 3.1.1.7
Source: Torpedo californica. Pacific electric ray. Organism_taxid: 7787. Variant: g2 form. Organ: electric organ. Tissue: electroplaque
Resolution:
2.20Å     R-factor:   0.168     R-free:   0.211
Authors: B.Sanson,F.Nachon,J.P.Colletier,M.T.Froment,L.Toker, H.M.Greenblatt,J.L.Sussman,Y.Ashani,P.Masson,I.Silman, M.Weik
Key ref: B.Sanson et al. (2009). Crystallographic snapshots of nonaged and aged conjugates of soman with acetylcholinesterase, and of a ternary complex of the aged conjugate with pralidoxime. J Med Chem, 52, 7593-7603. PubMed id: 19642642 DOI: 10.1021/jm900433t
Date:
15-Apr-09     Release date:   11-Aug-09    
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
Bound ligand (Het Group name = MES)
matches with 46.15% similarity
+ 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: 10.1021/jm900433t J Med Chem 52:7593-7603 (2009)
PubMed id: 19642642  
 
 
Crystallographic snapshots of nonaged and aged conjugates of soman with acetylcholinesterase, and of a ternary complex of the aged conjugate with pralidoxime.
B.Sanson, F.Nachon, J.P.Colletier, M.T.Froment, L.Toker, H.M.Greenblatt, J.L.Sussman, Y.Ashani, P.Masson, I.Silman, M.Weik.
 
  ABSTRACT  
 
Organophosphate compounds (OP) are potent inhibitors of acetylcholinesterases (AChEs) and can cause lethal poisoning in humans. Inhibition of AChEs by the OP soman involves phosphonylation of the catalytic serine, and subsequent dealkylation produces a form known as the "aged" enzyme. The nonaged form can be reactivated to a certain extent by nucleophiles, such as pralidoxime (2-PAM), whereas aged forms of OP-inhibited AChEs are totally resistant to reactivation. Here, we solved the X-ray crystal structures of AChE from Torpedo californica (TcAChE) conjugated with soman before and after aging. The absolute configuration of the soman stereoisomer adduct in the nonaged conjugate is P(S)C(R). A structural reorientation of the catalytic His440 side chain was observed during the aging process. Furthermore, the crystal structure of the ternary complex of the aged conjugate with 2-PAM revealed that the orientation of the oxime function does not permit nucleophilic attack on the phosphorus atom, thus providing a plausible explanation for its failure to reactivate the aged soman/AChE conjugate. Together, these three crystal structures provide an experimental basis for the design of new reactivators.