Binding Mode Investigations on the Interaction of
Lead(II) Acetate with Human Chorionic Gonadotropin
Hao Zhang
Yang Liu
Rui Zhang
Rutao Liu
Yadong Chen
10.1021/jp505565s.s001
https://acs.figshare.com/articles/journal_contribution/Binding_Mode_Investigations_on_the_Interaction_of_Lead_II_Acetate_with_Human_Chorionic_Gonadotropin/2264830
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 (<i>K</i><sub>SV</sub>) in the magnitude of 10<sup>3</sup> 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 (<i>Δ<i>H</i></i> < 0, <i>Δ<i>S</i></i> > 0) and hydrophobic forces (<i>Δ<i>H</i></i> > 0, <i>Δ<i>S</i></i> > 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.
2014-08-14 00:00:00
5 binding sites
Human Chorionic GonadotropinLead exposure
Fluorescence measurements
sex hormones
Binding Mode Investigations
KSV
collisional mechanism
Tyr residues
spectroscopic technique
UV
titration calorimetry
docking study
ELISA
docking results
310 K
ITC
dichroism spectroscopy
chorionic gonadotropin
HCG skeleton
acetate