title: The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis.
abstract: Human ferrochelatase (E.C. 4.99.1.1) is a homodimeric (86 kDa) mitochondrial membrane-associated enzyme that catalyzes the insertion of ferrous iron into protoporphyrin to form heme. We have determined the 2.0 A structure from the single wavelength iron anomalous scattering signal. The enzyme contains two NO-sensitive and uniquely coordinated [2Fe-2S] clusters. Its membrane association is mediated in part by a 12-residue hydrophobic lip that also forms the entrance to the active site pocket. The positioning of highly conserved residues in the active site in conjunction with previous biochemical studies support a catalytic model that may have significance in explaining the enzymatic defects that lead to the human inherited disease erythropoietic protoporphyria.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602-7229, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Wu
authors.forename: H A
authors.initials: HA
authors.lastname: Dailey
authors.forename: J P
authors.initials: JP
authors.lastname: Rose
authors.forename: A
authors.initials: A
authors.lastname: Burden
authors.forename: V M
authors.initials: VM
authors.lastname: Sellers
authors.forename: B C
authors.initials: BC
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D003902:Detergents / Q000378:metabolism; D019281:Dimerization; D005294:Ferrochelatase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006418:Heme / Q000096:biosynthesis*; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008670:Metals / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D017433:Protein Structure, Secondary; D016415:Sequence Alignment
chemical_list: D003902:Detergents; D007506:Iron-Sulfur Proteins; D008670:Metals; D006418:Heme; D005294:Ferrochelatase