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The 2.0 Å structure of human ferrochelatase, the terminal enzyme of heme biosynthesis

Nature Structural Biology volume 8, pages 156–160 (2001)Cite this article

Abstract

Human ferrochelatase (E.C. 4.99.1.1) is a homodimeric (86 kDa) mitochondrial membrane-associated enzyme that catalyzes the insertion of ferrous iron into protoporphyrin to form heme. We have determined the 2.0 Å structure from the single wavelength iron anomalous scattering signal. The enzyme contains two NO-sensitive and uniquely coordinated [2Fe-2S] clusters. Its membrane association is mediated in part by a 12-residue hydrophobic lip that also forms the entrance to the active site pocket. The positioning of highly conserved residues in the active site in conjunction with previous biochemical studies support a catalytic model that may have significance in explaining the enzymatic defects that lead to the human inherited disease erythropoietic protoporphyria.

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Figure 1: Structural features of HFc.
Figure 2: Structure of the HFc dimer.
Figure 3: A sectional view of the HFc active site pocket shown as a, a cartoon drawing and b, a ribbon drawing.

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Acknowledgements

We thank J. Ferrara and Molecular Structure Corporation, The Woodlands, Texas, for collecting the R-AXIS data, and M.K. Johnson for discussions concerning the cluster. This work was supported in part by a grant from the NIH to H.A.D., and funds from University of Georgia Research Foundation, and the Georgia Research Alliance to B.-C.W.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, University of Georgia, Athens, 30602-7229, Georgia, USA

    Chia-Kuei Wu, Harry A. Dailey, John P. Rose, Amy Burden, Vera M. Sellers & Bi-Cheng Wang

  2. Department of Crystallography, University of Pittsburgh, Pittsburgh, 15260, Pennsylvania, USA

    Chia-Kuei Wu

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  1. Chia-Kuei Wu
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  2. Harry A. Dailey
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Correspondence to Bi-Cheng Wang.

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Wu, CK., Dailey, H., Rose, J. et al. The 2.0 Å structure of human ferrochelatase, the terminal enzyme of heme biosynthesis. Nat Struct Mol Biol 8, 156–160 (2001). https://doi.org/10.1038/84152

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