PDBsum entry 2j4c

Hydrolase

PDB id: 2j4c

Contents

Protein chain

524 a.a. *

Ligands

NAG-NAG-FUC ×2

NAG ×3

SO4 ×2

GOL ×3

BUA

MES

Metals

_HG ×4

_CL ×3

Waters ×365

* Residue conservation analysis

PDB id:

2j4c

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

Resolution:

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

Date:

28-Aug-06 Release date: 27-Mar-07

Protein chain

P06276  (CHLE_HUMAN) -  Cholinesterase from Homo sapiens

Seq: 602 a.a.

Struc: 524 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.3.1.1.8 - cholinesterase.
• Reaction: an acylcholine + H2O = a carboxylate + choline + H⁺

acylcholine (Bound ligand (Het Group name = MES) matches with 46.67% similarity) + H2O = carboxylate (Bound ligand (Het Group name = BUA) matches with 42.86% similarity) + choline + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

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.

ABSTRACT

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.