PDBsum entry 2j4c

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protein ligands metals links
Hydrolase PDB id
Protein chain
524 a.a. *
NAG ×3
SO4 ×2
GOL ×3
_HG ×4
_CL ×3
Waters ×365
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Structure of human butyrylcholinesterase in complex with 10mm hgcl2
Structure: Cholinesterase. Chain: a. Synonym: acylcholine acylhydrolase, choline esterase ii, butyrylcholine esterase, pseudocholinesterase. Engineered: yes. Mutation: yes. Other_details: atypical bond between catalytic residue ser198 and ligand bty5 (butyrate)
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: cricetulus griseus. Expression_system_taxid: 10029. Expression_system_cell_line: ovary cells
2.75Å     R-factor:   0.184     R-free:   0.231
Authors: J.P.Colletier,M.F.Frasco,F.Carvalho,L.Guilhermino,J.Stojan, D.Fournier,M.Weik
Key ref: M.F.Frasco et al. (2007). Mechanisms of cholinesterase inhibition by inorganic mercury. FEBS J, 274, 1849-1861. PubMed id: 17355286
28-Aug-06     Release date:   27-Mar-07    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P06276  (CHLE_HUMAN) -  Cholinesterase
602 a.a.
524 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 4 residue positions (black crosses)

 Enzyme reactions 
   Enzyme class: E.C.  - Cholinesterase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: An acylcholine + H2O = choline + a carboxylate
Bound ligand (Het Group name = MES)
matches with 46.00% similarity
+ H(2)O
= choline
Bound ligand (Het Group name = BUA)
matches with 42.00% similarity
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   7 terms 
  Biological process     response to drug   13 terms 
  Biochemical function     catalytic activity     9 terms  


FEBS J 274:1849-1861 (2007)
PubMed id: 17355286  
Mechanisms of cholinesterase inhibition by inorganic mercury.
M.F.Frasco, J.P.Colletier, M.Weik, F.Carvalho, L.Guilhermino, J.Stojan, D.Fournier.
The poorly known mechanism of inhibition of cholinesterases by inorganic mercury (HgCl2) has been studied with a view to using these enzymes as biomarkers or as biological components of biosensors to survey polluted areas. The inhibition of a variety of cholinesterases by HgCl2 was investigated by kinetic studies, X-ray crystallography, and dynamic light scattering. Our results show that when a free sensitive sulfhydryl group is present in the enzyme, as in Torpedo californica acetylcholinesterase, inhibition is irreversible and follows pseudo-first-order kinetics that are completed within 1 h in the micromolar range. When the free sulfhydryl group is not sensitive to mercury (Drosophila melanogaster acetylcholinesterase and human butyrylcholinesterase) or is otherwise absent (Electrophorus electricus acetylcholinesterase), then inhibition occurs in the millimolar range. Inhibition follows a slow binding model, with successive binding of two mercury ions to the enzyme surface. Binding of mercury ions has several consequences: reversible inhibition, enzyme denaturation, and protein aggregation, protecting the enzyme from denaturation. Mercury-induced inactivation of cholinesterases is thus a rather complex process. Our results indicate that among the various cholinesterases that we have studied, only Torpedo californica acetylcholinesterase is suitable for mercury detection using biosensors, and that a careful study of cholinesterase inhibition in a species is a prerequisite before using it as a biomarker to survey mercury in the environment.

Literature references that cite this PDB file's key reference

  PubMed id Reference
19874286 J.Valentini, J.Vicentini, D.Grotto, R.Tonello, S.C.Garcia, and F.Barbosa (2010).
Sub-chronic exposure to methylmercury at low levels decreases butyrylcholinesterase activity in rats.
  Basic Clin Pharmacol Toxicol, 106, 95-99.  
19778721 M.V.Yigit, A.Mishra, R.Tong, J.Cheng, G.C.Wong, and Y.Lu (2009).
Inorganic mercury detection and controlled release of chelating agents from ion-responsive liposomes.
  Chem Biol, 16, 937-942.  
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