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Structure and function of ferrochelatase

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Abstract

Ferrochelatase is the terminal enzyme of the heme biosynthetic pathway in all cells. It catalyzes the insertion of ferrous iron into protoporphyrin IX, yielding heme. In eukaryotic cells, ferrochelatase is a mitochondrial inner membrane-associated protein with the active site facing the matrix. Decreased values of ferrochelatase activity in all tissues are a characteristic of patients with protoporphyria. Point-mutations in the ferrochelatase gene have been recently found to be associated with certain cases of erythropoietic protoporphyria. During the past four years, there have been considerable advances in different aspects related to structure and function of ferrochelatase. Genomic and cDNA clones for bacteria, yeast, barley, mouse, and human ferrochelatase have been isolated and sequenced. Functional expression of yeast ferrochelatase in yeast strains deficient in this enzyme, and expression inEscherichia coli and in baculovirusinfected insect cells of different ferrochelatase cDNAs have been accomplished. A recently identified (2Fe-2S) cluster appears to be a structural feature shared among mammalian ferrochelatases. Finally, functional studies of ferrochelatase site-directed mutants, in which key amino acids were replaced with residues identified in some cases of protoporphyria, will be summarized in the context of protein structure.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, 33612, Tampa, Florida

    Gloria C. Ferreira

  2. Institute for Biomolecular Science, University of South Florida, 33612, Tampa, Florida

    Gloria C. Ferreira

  3. The H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, 33612, Tampa, Florida

    Gloria C. Ferreira

  4. Centro de Química Fina e Biotecnologia, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2825, Monte de Caparica, Portugal

    Ricardo Franco, Isabel Moura & José J. G. Moura

  5. Department of Physics, Emory University, 30322, Atlanta, Georgia

    Steven G. Lloyd & Boi H. Huynh

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  1. Gloria C. Ferreira
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Ferreira, G.C., Franco, R., Lloyd, S.G. et al. Structure and function of ferrochelatase. J Bioenerg Biomembr 27, 221–229 (1995). https://doi.org/10.1007/BF02110037

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