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Interactions of uranyl ion with cytochrome b 5 and its His39Ser variant as revealed by molecular simulation in combination with experimental methods

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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.

Impacts of uranyl ion on the structure and function of cytochrome b5 H39S variant

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Acknowledgments

We gratefully thank Prof. Zhong-Xian Huang at Fudan University, Shanghai, China, for providing the cytochrome b 5 gene and proteins, and Dr. Tianlei Ying at the National Institutes of Health (NIH), USA, for discussions regarding simulation of the uranyl ion. NAMD and VMD were developed by the Theoretical Biophysics Group in the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign, USA. This work is supported by the National Natural Science Foundation of China (NSFC Nos. 20877038, 10975069).

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Authors and Affiliations

  1. School of Chemistry and Chemical Engineering, University of South China, Hengyang, 421001, People’s Republic of China

    Dun Wan, Li-Fu Liao, Min-Min Zhao, Min-Long Wu & Ying-Wu Lin

  2. Institute of Pathogenic Biology, University of South China, Hengyang, 421001, People’s Republic of China

    Yi-Mou Wu

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  1. Dun Wan
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  2. Li-Fu Liao
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  3. Min-Min Zhao
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  4. Min-Long Wu
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Correspondence to Ying-Wu Lin.

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Wan, D., Liao, LF., Zhao, MM. et al. Interactions of uranyl ion with cytochrome b 5 and its His39Ser variant as revealed by molecular simulation in combination with experimental methods. J Mol Model 18, 1009–1013 (2012). https://doi.org/10.1007/s00894-011-1097-1

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