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Crystal structure of rat biliverdin reductase

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Abstract

Biliverdin reductase (BVR) is a soluble cytoplasmic enzyme that catalyzes the conversion of biliverdin to bilirubin using NADH or NADPH as electron donor. Bilirubin is a significant biological antioxidant, but it is also neurotoxic and the cause of kernicterus. In this study, we have determined the crystal structure of rat BVR at 1.4 Å resolution. The structure contains two domains: an N-terminal domain characteristic of a dinucleotide binding fold (Rossmann fold) and a C-terminal domain that is predominantly an antiparallel six-stranded β-sheet. Based on this structure, we propose modes of binding for NAD(P)H and biliverdin, and a possible mechanism for the enzyme.

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Figure 1: Heme degradation pathway in mammals.
Figure 2: Structure and amino acid sequence of rat BVR.
Figure 3: The proposed BVR cofactor and substrate binding site.

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Acknowledgements

This work was supported in part by grants from the Structural Biology and the MR Science Programs in RIKEN (to Y.S.), and the Special Postdoctoral Researchers Program in RIKEN (to A.K.). We thank S. Adachi and H. Shimizu for diffraction data processing and also A.F. McDonagh for careful reading of the manuscript and helpful comments.

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Authors and Affiliations

  1. RIKEN Harima Institute/SPring-8, Sayo, 679-5148, Hyogo, Japan

    Akihiro Kikuchi, Sam-Yong Park, Hideyuki Miyatake & Yoshitsugu Shiro

  2. Department of Biochemistry, Yamagata University School of Medicine, Yamagata, 990-9585, Japan

    Danyu Sun & Tadashi Yoshida

  3. Central Laboratory for Research and Education, Yamagata University School of Medicine, Yamagata, 990-9585, Japan

    Michihiko Sato

Authors
  1. Akihiro Kikuchi
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  2. Sam-Yong Park
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  3. Hideyuki Miyatake
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  4. Danyu Sun
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  5. Michihiko Sato
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  6. Tadashi Yoshida
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  7. Yoshitsugu Shiro
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Correspondence to Akihiro Kikuchi.

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Kikuchi, A., Park, SY., Miyatake, H. et al. Crystal structure of rat biliverdin reductase. Nat Struct Mol Biol 8, 221–225 (2001). https://doi.org/10.1038/84955

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  • DOI: https://doi.org/10.1038/84955

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