The 2.0 A structure of human ferrochelatase, the terminal enzyme of heme biosynthesis

Nat Struct Biol. 2001 Feb;8(2):156-60. doi: 10.1038/84152.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Catalysis
  • Crystallography, X-Ray
  • Detergents / metabolism
  • Dimerization
  • Ferrochelatase / chemistry*
  • Ferrochelatase / genetics
  • Ferrochelatase / metabolism*
  • Heme / biosynthesis*
  • Humans
  • Iron-Sulfur Proteins / chemistry
  • Iron-Sulfur Proteins / genetics
  • Iron-Sulfur Proteins / metabolism
  • Metals / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation / genetics
  • Protein Structure, Secondary
  • Sequence Alignment

Substances

  • Detergents
  • Iron-Sulfur Proteins
  • Metals
  • Heme
  • Ferrochelatase

Associated data

  • PDB/1HRK