2J4C

Structure of human Butyrylcholinesterase in complex with 10mM HgCl2

Summary for 2J4C

• Entry DOI: 10.2210/pdb2j4c/pdb
• Related: 1EHO 1EHQ 1KCJ 1P0I 1P0M 1P0P 1P0Q 1XLU 1XLV 1XLW
• Descriptor: CHOLINESTERASE, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• Functional Keywords: hydrolase, inhibition, glycoprotein, polymorphism, inorganic mercury, cholinesterase, serine esterase, disease mutation
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 63153.70

Authors

Colletier, J.P.,Frasco, M.F.,Carvalho, F.,Guilhermino, L.,Stojan, J.,Fournier, D.,Weik, M. (deposition date: 2006-08-28, release date: 2007-03-27, Last modification date: 2023-12-13)

Primary citation

Frasco, M.F.,Colletier, J.,Weik, M.,Carvalho, F.,Guilhermino, L.,Stojan, J.,Fournier, D.
Mechanisms of Cholinesterase Inhibition by Inorganic Mercury.
FEBS J., 274:1849-, 2007

PubMed 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.

PubMed: 17355286
DOI: 10.1111/J.1742-4658.2007.05732.X

Experimental method

X-RAY DIFFRACTION (2.75 Å)