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Binding Mode Investigations on the Interaction of Lead(II) Acetate with Human Chorionic Gonadotropin
journal contribution
posted on 2014-08-14, 00:00 authored by Hao Zhang, Yang Liu, Rui Zhang, Rutao Liu, Yadong ChenLead 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 103 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.
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Keywords
5 binding sitesHuman Chorionic GonadotropinLead exposureFluorescence measurementssex hormonesBinding Mode InvestigationsKSVcollisional mechanismTyr residuesspectroscopic techniqueUVtitration calorimetrydocking studyELISAdocking results310 KITCdichroism spectroscopychorionic gonadotropinHCG skeletonacetate
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