title: Interactions of uranyl ion with cytochrome b₅ and its His39Ser variant as revealed by molecular simulation in combination with experimental methods.
abstract: The biological toxicity of uranyl ion (UO (2) (2+) ) lies in interacting with proteins and disrupting their native functions. The structural and functional consequences of UO (2) (2+) interacting with cytochrome b (5) (cyt b (5)), a small membrane heme protein, and its heme axial ligand His39Ser variant, cyt b (5) H39S, were investigated both experimentally and theoretically. In experiments, although cyt b (5) was only slightly affected, UO (2) (2+) binding to cyt b (5) H39S with a K (D) of 2.5 μM resulted in obvious alteration of the heme active site, and led to a decrease in peroxidase activity. Theoretically, molecular simulation proposed a uranyl ion binding site for cyt b (5) at surface residues of Glu37 and Glu43, revealing both coordination and hydrogen bonding interactions. The information gained in this study provides insights into the mechanism of uranyl toxicity toward membrane protein at an atomic level.
authors.affiliation: School of Chemistry and Chemical Engineering, University of South China, Hengyang 421001, People's Republic of China.
authors.forename: Dun
authors.initials: D
authors.lastname: Wan
authors.forename: Li-Fu
authors.initials: LF
authors.lastname: Liao
authors.forename: Min-Min
authors.initials: MM
authors.lastname: Zhao
authors.forename: Min-Long
authors.initials: ML
authors.lastname: Wu
authors.forename: Yi-Mou
authors.initials: YM
authors.lastname: Wu
authors.forename: Ying-Wu
authors.initials: YW
authors.lastname: Lin
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D015786:Cytochromes b5 / Q000737:chemistry* / Q000235:genetics*; D014644:Genetic Variation; D006418:Heme; D006860:Hydrogen Bonding; D007477:Ions; D007700:Kinetics; D008958:Models, Molecular; D020125:Mutation, Missense; D011485:Protein Binding; D014501:Uranium / Q000737:chemistry* / Q000633:toxicity
chemical_list: D007477:Ions; D006418:Heme; D014501:Uranium; D015786:Cytochromes b5