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Blood, 1 August 2005, Vol. 106, No. 3, pp. 1098-1104. Prepublished online as a Blood First Edition Paper on April 14, 2005; DOI 10.1182/blood-2004-12-4661. This Article Full Text (PDF) All Versions of this Article: 2004-12-4661v1 106/3/1098    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Najahi-Missaoui, W. Articles by Dailey, H. A Search for Related Content PubMed PubMed Citation Articles by Najahi-Missaoui, W. Articles by Dailey, H. A Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 9, 2004 Accepted April 8, 2005 Production and characterization of erythropoietic protoporphyric heterodimeric ferrochelatases Wided Najahi-Missaoui and Harry A Dailey* Biomedical and Health Sciences Institute, University of Georgia, Athens, Georgia, USA Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, USA * Corresponding author; email: hdailey{at}uga.edu. Mutations resulting in diminished activity of the dimeric enzyme ferrochelatase are a prerequisite for the inherited disorder erythropoietic protoporphyria (EPP). Patients with clinical EPP have only 10-30% of normal levels of ferrochelatase activity and while many EPP patients possess one mutant allele and one 'low expression' normal allele, the possibility remains that for some, low ferrochelatase activity may result from an EPP mutation that has an impact on both subunits of the wild-type/mutant heterodimer. Herein we present data for twelve ferrochelatase wild-type/EPP mutant heterodimers showing that some mutations result in heterodimers with the residual activity anticipated from individual constituents, while others result in heterodimers with significantly lower activity than would be predicted. While the data do not allow an a priori prediction of heterodimeric residual activity based solely upon in vitro activity of EPP homodimers or position of the mutated residue within ferrochelatase, mutations that affect the dimer interface or [2Fe-2S] cluster have a significantly greater impact on residual activity than would be predicted. These data suggest that some EPP mutations may result in clinically overt EPP in the absence of a low expression wild-type allele and this is of potential significance for genetic counseling of EPP patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: G. A. Hunter, M. P. Sampson, and G. C. Ferreira Metal Ion Substrate Inhibition of Ferrochelatase J. Biol. Chem., August 29, 2008; 283(35): 23685 - 23691. [Abstract] [Full Text] [PDF]

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