Ferrochelatase, N-terminal (IPR033659)

Short name: Ferrochelatase_N

Overlapping homologous superfamilies


Domain relationships



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 [PMID: 12196143, PMID: 11215517, PMID: 10582332, PMID: 8122254, PMID: 6390167, PMID: 7592569, PMID: 11175906, PMID: 12427010, PMID: 10704318, PMID: 12761666, PMID: 2185242, PMID: 1704134]. 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 [PMID: 9384565, PMID: 11175906]. The human enzyme exists as a homodimer. Each subunit contains one [2Fe-2S] cluster. The monomer is folded into two similar domains, each with a four-stranded parallel beta-sheet flanked by an alpha-helix in a beta-alpha-beta motif that is reminiscent of the fold found in the periplasmic binding proteins. The topological similarity between the domains suggests that they have arisen from a gene duplication event. However, significant differences exist between the two domains, including an N-terminal section (residues 80-130) that forms part of the active site pocket, and a C-terminal extension (residues 390-423) that is involved in coordination of the [2Fe-2S] cluster and in stabilisation 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 [PMID: 9384565].

This entry represents the N-terminal domain of ferrochelatase.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.