2J4C

Structure of human Butyrylcholinesterase in complex with 10mM HgCl2

2J4C の概要

• エントリーDOI: 10.2210/pdb2j4c/pdb
• 関連するPDBエントリー: 1EHO 1EHQ 1KCJ 1P0I 1P0M 1P0P 1P0Q 1XLU 1XLV 1XLW
• 分子名称: 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)
• 機能のキーワード: hydrolase, inhibition, glycoprotein, polymorphism, inorganic mercury, cholinesterase, serine esterase, disease mutation
• 由来する生物種: HOMO SAPIENS (HUMAN)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 63153.70

構造登録者

Colletier, J.P.,Frasco, M.F.,Carvalho, F.,Guilhermino, L.,Stojan, J.,Fournier, D.,Weik, M. (登録日: 2006-08-28, 公開日: 2007-03-27, 最終更新日: 2023-12-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.75 Å)