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PDBsum entry 2jey

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protein ligands Protein-protein interface(s) links
Hydrolase PDB id
2jey
Jmol
Contents
Protein chains
535 a.a. *
Ligands
HLO ×2
P6G
Waters ×162
* Residue conservation analysis
PDB id:
2jey
Name: Hydrolase
Title: Mus musculus acetylcholinesterase in complex with hlo-7
Structure: Acetylcholinesterase. Chain: a, b. Fragment: catalytic domain, residues 32-574. Synonym: ache. Engineered: yes
Source: Mus musculus. Mouse. Organism_taxid: 10090. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293.
Resolution:
2.70Å     R-factor:   0.207     R-free:   0.261
Authors: F.Ekstrom,C.Astot,Y.P.Pang
Key ref: F.J.Ekström et al. (2007). Novel nerve-agent antidote design based on crystallographic and mass spectrometric analyses of tabun-conjugated acetylcholinesterase in complex with antidotes. Clin Pharmacol Ther, 82, 282-293. PubMed id: 17443135
Date:
25-Jan-07     Release date:   03-Jul-07    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P21836  (ACES_MOUSE) -  Acetylcholinesterase
Seq:
Struc:
 
Seq:
Struc:
614 a.a.
535 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
+ 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     extracellular region   17 terms 
  Biological process     synapse assembly   13 terms 
  Biochemical function     carboxylic ester hydrolase activity     9 terms  

 

 
    reference    
 
 
Clin Pharmacol Ther 82:282-293 (2007)
PubMed id: 17443135  
 
 
Novel nerve-agent antidote design based on crystallographic and mass spectrometric analyses of tabun-conjugated acetylcholinesterase in complex with antidotes.
F.J.Ekström, C.Astot, Y.P.Pang.
 
  ABSTRACT  
 
Organophosphorus compound-based nerve agents inhibit the essential enzyme acetylcholinesterase (AChE) causing acute toxicity and death. Clinical treatment of nerve-agent poisoning is to use oxime-based antidotes to reactivate the inhibited AChE. However, the nerve agent tabun is resistant to oximes. To design improved oximes, crystal structures of a tabun-conjugated AChE in complex with different oximes are needed to guide the structural modifications of known antidotes. However, this type of structure is extremely challenging to obtain because both deamidation of the tabun conjugate and reactivation of AChE occur during crystallographic experiments. Here we report, for the first time, the crystal structures of Ortho-7 and HLö-7 in complex with AChE that is conjugated to an intact tabun. These structures were determined by our new strategy of combining crystallographic and mass spectrometric analyses of AChE crystals. The results explain the relative reactivation potencies of the two oximes and offer insights into improving known medical antidotes.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
21397501 M.Komloova, K.Musilek, A.Horova, O.Holas, V.Dohnal, F.Gunn-Moore, and K.Kuca (2011).
Preparation, in vitro screening and molecular modelling of symmetrical bis-quinolinium cholinesterase inhibitors--implications for early myasthenia gravis treatment.
  Bioorg Med Chem Lett, 21, 2505-2509.  
20140002 M.K.Kesharwani, B.Ganguly, A.Das, and T.Bandyopadhyay (2010).
Differential binding of bispyridinium oxime drugs with acetylcholinesterase.
  Acta Pharmacol Sin, 31, 313-328.  
20004171 P.Masson, and O.Lockridge (2010).
Butyrylcholinesterase for protection from organophosphorus poisons: catalytic complexities and hysteretic behavior.
  Arch Biochem Biophys, 494, 107-120.  
19368529 E.Carletti, N.Aurbek, E.Gillon, M.Loiodice, Y.Nicolet, J.C.Fontecilla-Camps, P.Masson, H.Thiermann, F.Nachon, and F.Worek (2009).
Structure-activity analysis of aging and reactivation of human butyrylcholinesterase inhibited by analogues of tabun.
  Biochem J, 421, 97.
PDB codes: 2wid 2wif 2wig 2wij 2wik 2wil 2wsl
19536291 F.Ekström, A.Hörnberg, E.Artursson, L.G.Hammarström, G.Schneider, and Y.P.Pang (2009).
Structure of HI-6*sarin-acetylcholinesterase determined by X-ray crystallography and molecular dynamics simulation: reactivator mechanism and design.
  PLoS One, 4, e5957.
PDB codes: 2whp 2whq 2whr
19714254 Y.P.Pang, F.Ekström, G.A.Polsinelli, Y.Gao, S.Rana, D.H.Hua, B.Andersson, P.O.Andersson, L.Peng, S.K.Singh, R.K.Mishra, K.Y.Zhu, A.M.Fallon, D.W.Ragsdale, and S.Brimijoin (2009).
Selective and irreversible inhibitors of mosquito acetylcholinesterases for controlling malaria and other mosquito-borne diseases.
  PLoS One, 4, e6851.
PDB code: 2wls
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.