The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis.
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.
Wu
C K
CK
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602-7229, USA.
Dailey
H A
HA
Rose
J P
JP
Burden
A
A
Sellers
V M
VM
Wang
B C
BC
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
D003902:Detergents; D007506:Iron-Sulfur Proteins; D008670:Metals; D006418:Heme; D005294:Ferrochelatase