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Crystal structure of human heme oxygenase-1

Nature Structural Biology volume 6, pages 860–867 (1999)Cite this article

Abstract

Heme oxygenase catalyzes the first step in the oxidative degradation of heme. The crystal structure of heme oxygenase-1 (HO-1) reported here reveals a novel helical fold with the heme sandwiched between two helices. The proximal helix provides a heme iron ligand, His 25. Conserved glycines in the distal helix near the oxygen binding site allow close contact between the helix backbone and heme in addition to providing flexibility for substrate binding and product release. Regioselective oxygenation of the α-meso heme carbon is due primarily to steric influence of the distal helix.

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Figure 1
Figure 2: The overall structure of HO-1.
Figure 3: Solvent-accessible surfaces of HO-1 colored by electrostatic potential (negative is red, positive is blue).
Figure 4: The active site of HO-1.
Figure 5: Flexibility and alternate conformations of the two molecules in the asymmetric unit.
Figure 6: a, Plot of the r.m.s. deviation of backbone atoms between the two molecules in the asymmetric unit.

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Acknowledgements

Thanks to S. Tajbaksh for help with protein purification, to J.P. Cartailler for help with the GRASP figures, to B. Bhaskar, W.N. Lanzilotta, H. Li, C.S. Raman, I. Sevrioukova and M. Sundaramoorthy for helpful discussions, and to A. J. Greenwood for computational assistance. This work was supported by grants from the National Institutes of Health (T.L.P. and P.R.O.d.M.) and the National Science Foundation (T.L.P.).

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  1. Angela Wilks

    Present address: Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland, 21201-1180, USA

Authors and Affiliations

  1. Departments of Molecular Biology and Biochemistry, and Physiology and Biophysics, and Program in Macromolecular Structure, University of California, Irvine, 92697-3900, California, USA

    David J. Schuller & Thomas L. Poulos

  2. Department of Pharmaceutical Chemistry, University of California, San Francisco, 94143-0446, California, USA

    Angela Wilks & Paul R. Ortiz de Montellano

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Correspondence to Thomas L. Poulos.

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Schuller, D., Wilks, A., Ortiz de Montellano, P. et al. Crystal structure of human heme oxygenase-1. Nat Struct Mol Biol 6, 860–867 (1999). https://doi.org/10.1038/12319

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