In vitro and in silico investigations of the binding interactions between chlorophenols and trypsin
Yan-Qing Wang1, Chun-Yun Tan2, Shu-Lin Zhuang3
1Jiangsu Provincial Key Laboratory of Coastal Wetland Bioresources and Environmental Protection, Yancheng City 224002, Jiangsu Province, People's Republic of China; Institute of Applied Chemistry and Environmental Engineering, Yancheng Teachers University, Yancheng City 224002, Jiangsu Province, People's Republic of China.
Abstract:
Being the first-degree toxic pollutants, chlorophenols (CP) have potential carcinogenic and mutagenic activity and toxicity. Since there still lacks studies on molecular interactions of chlorophenols with trypsin, one major binding target of many exogenous environmental pollutants, the binding interactions between five chlorophenols, 2-CP, 2,6-DCP, 2,4,6-TCP, 2,4,6-TCP, 2,3,4,6-TCP and PCP and trypsin were characterized by the combination of multispectroscopic techniques and molecular modeling. The chlorophenols bind at the one main site of trypsin and the binding induces the changes of microenvironment and global conformations of trypsin. Different number of chloride atoms significantly affects the binding and the binding constants KA ranks as KA (2-CP) < KA (2,6-DCP) ≈ KA (2,4,6-TCP) < KA (2,3,4,6-TCP) < KA (PCP). These chlorophenols interacts with trypsin mainly through hydrophobic interactions and via hydrogen bonding interactions and aromatic-aromatic π-π stacking interaction. Our results offer insights into the binding mechanism of chlorophenols with trypsin and provide important information for possible toxicity risk of chlorophenols to human health.
Insights
Chlorophenols (CPs) bind to trypsin, altering its structure and function. The number of chlorine atoms influences binding affinity, revealing potential human health risks from these toxic pollutants.
Area of Science:
- Environmental Chemistry
- Biochemistry
- Toxicology
Background:
- Chlorophenols (CPs) are toxic pollutants with carcinogenic and mutagenic potential.
- Limited research exists on the molecular interactions between CPs and trypsin, a key binding target for environmental contaminants.
Purpose of the Study:
- To investigate the binding interactions between five chlorophenols and trypsin.
- To elucidate the binding mechanism and identify factors influencing binding affinity.
Main Methods:
- Utilized multispectroscopic techniques (e.g., fluorescence spectroscopy, UV-Vis absorption).
- Employed molecular modeling to simulate binding interactions.
- Quantified binding constants (KA) for different chlorophenols.
Main Results:
- Chlorophenols bind to a primary site on trypsin, inducing conformational changes.
- Binding affinity is influenced by the number of chlorine atoms, with higher chlorination leading to stronger binding (KA (2-CP) < KA (2,6-DCP) ≈ KA (2,4,6-TCP) < KA (2,3,4,6-TCP) < KA (PCP)).
- Interactions involve hydrophobic forces, hydrogen bonding, and aromatic π-π stacking.
Conclusions:
- Established the binding mechanism of chlorophenols to trypsin.
- Provided crucial data on the toxicity risk of chlorophenols to human health due to their interaction with biological targets.
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