title: Binding mode investigations on the interaction of lead(II) acetate with human chorionic gonadotropin.
abstract: Lead exposure could induce endocrine disruption and hormonal imbalance of humans, resulting in detrimental effects on the reproductive system even at low doses. However, mechanisms of lead actions remain unknown. This article investigated lead interactions with human chorionic gonadotropin (HCG) as a conceivable mechanism of its reproductive toxicity by spectroscopic technique, isothermal titration calorimetry (ITC), molecular docking study, and enzyme-linked immunosorbent assay (ELISA). Fluorescence measurements showed that lead acetate dynamically quenched intrinsic fluorescence of HCG through collisional mechanism with the association constant (KSV) in the magnitude of 10(3) L/mol at the detected temperatures (298, 303, and 310 K). ITC and molecular docking results revealed lead acetate could bind into 5 binding sites of HCG through electrostatic effects (ΔH < 0, ΔS > 0) and hydrophobic forces (ΔH > 0, ΔS > 0). The conformational investigation of HCG by UV-vis absorption spectroscopy, circular dichroism spectroscopy, and ELISA indicated lead acetate changed the secondary structure of HCG by loosening and destruction of HCG skeleton and increasing the hydrophobicity around Tyr residues and resulted in the decreased bioactivities of HCG. This work presents direct interactions of lead with sex hormones and obtains a possible mechanism on lead induced reproductive toxicity at the molecular level.
authors.affiliation: School of Environmental Science and Engineering, Shandong University , 27 Shanda Nanlu, Jinan 250100, P. R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.forename: Rutao
authors.initials: R
authors.lastname: Liu
authors.forename: Yadong
authors.initials: Y
authors.lastname: Chen
mesh_terms: D001665:Binding Sites; D002151:Calorimetry; D006063:Chorionic Gonadotropin / Q000737:chemistry*; D004797:Enzyme-Linked Immunosorbent Assay; D005453:Fluorescence; D006801:Humans; D062105:Molecular Docking Simulation; D009942:Organometallic Compounds / Q000737:chemistry*; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D006063:Chorionic Gonadotropin; D009942:Organometallic Compounds; C008261:lead acetate