InterPro domain: IPR001015

Synonym(s): Protohaem ferro-lyase, Iron chelatase, etc.

Ferrochelatase is the terminal enzyme of the heme biosynthetic pathway. It catalyzes the insertion of ferrous iron into the protoporphyrin IX ring yielding protoheme. This enzyme is ubiquitous in nature and widely distributed in bacteria and eukaryotes. Recently, some archaeal members have been identified. The oligomeric state of these enzymes varies depending on the presence of a dimerization motif at the C terminus [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. In eukaryotic cells, it binds to the mitochondrial inner membrane with its active site on the matrix side of the membrane.

The X-ray structure of Bacillus subtilis and human ferrochelatase have been solved [ 13 , 14 ].The human enzyme exists as a homodimer. Eachsubunit contains one [2Fe-2S] cluster. The monomer is folded into twosimilar domains, each with a four-stranded parallelbeta-sheet flanked by an alpha-helix in a beta-alpha-beta motif that isreminiscent of the fold found in the periplasmic bindingproteins. The topological similarity between the domains suggests thatthey have arisen from a gene duplication event. However,significant differences exist between the two domains, including anN-terminal section (residues 80-130) that forms part of theactive site pocket, and a C-terminal extension (residues 390-423) thatis involved in coordination of the [2Fe-2S] cluster and instabilisation of the homodimer.

Ferrochelatase seems to have a structurally conserved core region that is common to the enzyme from bacteria, plants and mammals. Porphyrin binds in the identified cleft; this cleft also includes the metal-binding site of the enzyme. It is likely that the structure of the cleft region will have different conformations upon substrate binding and release [ 14 ].

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4. Molecular and genetic characterization of ferrochelatase. Tohoku J. Exp. Med. 171, 1-20
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8. Metal binding to Saccharomyces cerevisiae ferrochelatase. Biochemistry 41, 13499-506
9. Structural and mechanistic basis of porphyrin metallation by ferrochelatase. J. Mol. Biol. 297, 221-32
10. Metal binding to Bacillus subtilis ferrochelatase and interaction between metal sites. J. Biol. Inorg. Chem. 8, 452-8
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12. Cloning of murine ferrochelatase. Proc. Natl. Acad. Sci. U.S.A. 88, 849-53
13. Crystal structure of ferrochelatase: the terminal enzyme in heme biosynthesis. Structure 5, 1501-10