Crystal structure of rat haem oxygenase-1 in complex with ferrous verdohaem: presence of a hydrogen-bond network on the distal side

Abstract

HO (haem oxygenase) catalyses the degradation of haem to biliverdin, CO and ferrous iron via three successive oxygenation reactions, i.e. haem to α-hydroxyhaem, α-hydroxyhaem to α-verdohaem and α-verdohaem to ferric biliverdin–iron chelate. In the present study, we determined the crystal structure of ferrous α-verdohaem–rat HO-1 complex at 2.2 Å (1 Å=0.1 nm) resolution. The overall structure of the verdohaem complex was similar to that of the haem complex. Water or OH− was co-ordinated to the verdohaem iron as a distal ligand. A hydrogen-bond network consisting of water molecules and several amino acid residues was observed at the distal side of verdohaem. Such a hydrogen-bond network was conserved in the structures of rat HO-1 complexes with haem and with the ferric biliverdin–iron chelate. This hydrogen-bond network may act as a proton donor to form an activated oxygen intermediate, probably a ferric hydroperoxide species, in the degradation of α-verdohaem to ferric biliverdin–iron chelate similar to that seen in the first oxygenation step.