Ferreira G C, Franco R, Lloyd S G, Moura I, Moura J J, Huynh B H
Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa 33612, USA.
J Bioenerg Biomembr. 1995 Apr;27(2):221-9. doi: 10.1007/BF02110037.
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 in Escherichia coli and in baculovirus-infected 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.
亚铁螯合酶是所有细胞中血红素生物合成途径的末端酶。它催化亚铁离子插入原卟啉IX中，生成血红素。在真核细胞中，亚铁螯合酶是一种与线粒体内膜相关的蛋白质，其活性位点面向线粒体基质。所有组织中亚铁螯合酶活性值降低是原卟啉症患者的一个特征。最近发现亚铁螯合酶基因中的点突变与某些红细胞生成性原卟啉症病例有关。在过去四年中，与亚铁螯合酶的结构和功能相关的不同方面都取得了相当大的进展。已经分离并测序了细菌、酵母、大麦、小鼠和人类亚铁螯合酶的基因组和cDNA克隆。在缺乏该酶的酵母菌株中实现了酵母亚铁螯合酶的功能表达，并在大肠杆菌和杆状病毒感染的昆虫细胞中实现了不同亚铁螯合酶cDNA的表达。最近鉴定出的一个（2Fe-2S）簇似乎是哺乳动物亚铁螯合酶共有的一种结构特征。最后，将在蛋白质结构的背景下总结对亚铁螯合酶定点突变体的功能研究，在这些突变体中，关键氨基酸被原卟啉症某些病例中鉴定出的残基所取代。
