title: Investigations on the effects of Cu(2+) on the structure and function of human serum albumin.
abstract: Human serum albumin (HSA) is the most prominent protein in blood plasma with important physiological functions. Although copper is an essential metal for all organisms, the massive utilization of copper has led to concerns regarding its potential health impact. To better understand the potential toxicity and toxic mechanisms of Cu(2+), it is of vital importance to characterize the interaction of Cu(2+) with HSA. The effect of Cu(2+) on the structure and function of HSA in vitro were investigated by biophysical methods including fluorescence techniques, circular dichroism (CD), time-resolved measurements, isothermal titration calorimetry (ITC), molecular simulations and esterase activity assay. Multi-spectroscopic measurements proved that Cu(2+) quenched the intrinsic fluorescence of HSA in a dynamic process accompanied by the formation of complex and alteration of secondary structure. But the Cu(2+) had minimal effect on the backbone and secondary structure of HSA at relatively low concentrations. The ITC results indicated Cu(2+) interacted with HSA spontaneously through hydrophobic forces with approximately 1 thermodynamic identical binding sites at 298 K. The esterase activity of HSA was inhibited obviously at the concentration of 8 × 10(-5) M. However, molecular simulation showed that Cu(2+) mainly interacted with the amino acid residues Asp (451) by the electrostatic force. Thus, we speculated the interaction between Cu(2+) and HSA might induce microenvironment of the active site (Arg 410). This study has provided a novel idea to explore the biological toxicity of Cu(2+) at the molecular level.
authors.affiliation: School of Environmental Science and Engineering, Shandong University, China -America CRC for Environment & Health, Shandong Province, 27 Shanda Nanlu, Jinan, 250100, China.
authors.forename: Mingyang
authors.initials: M
authors.lastname: Jing
authors.affiliation: School of Environmental Science and Engineering, Shandong University, China -America CRC for Environment & Health, Shandong Province, 27 Shanda Nanlu, Jinan, 250100, China.
authors.forename: Rutao
authors.initials: R
authors.lastname: Liu
authors.affiliation: School of Environmental Science and Engineering, Shandong University, China -America CRC for Environment & Health, Shandong Province, 27 Shanda Nanlu, Jinan, 250100, China.
authors.forename: Wenbao
authors.initials: W
authors.lastname: Yan
authors.affiliation: School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, Jinan, Shandong Province, 250353, P.R. China.
authors.forename: Xuejie
authors.initials: X
authors.lastname: Tan
authors.affiliation: Laboratory of Molecular Design and Drug Discovery, School of Basic Science, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Chen
mesh_terms: D002151:Calorimetry; D003300:Copper / Q000737:chemistry* / Q000378:metabolism; D005453:Fluorescence; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D012709:Serum Albumin; D003300:Copper
keywords: Cu2+; human serum albumin; interaction mechanisms; toxicity assessment