Crystal structure of rat haem oxygenase-1 in complex with ferrous verdohaem: presence of a hydrogen-bond network on the distal side.
HO (haem oxygenase) catalyses the degradation of haem to biliverdin, CO and ferrous iron via three successive oxygenation reactions, i.e. haem to alpha-hydroxyhaem, alpha-hydroxyhaem to alpha-verdohaem and alpha-verdohaem to ferric biliverdin-iron chelate. In the present study, we determined the crystal structure of ferrous alpha-verdohaem-rat HO-1 complex at 2.2 A (1 A=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 alpha-verdohaem to ferric biliverdin-iron chelate similar to that seen in the first oxygenation step.
Sato
Hideaki
H
Department of Medical Biochemistry, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan.
Sugishima
Masakazu
M
Sakamoto
Hiroshi
H
Higashimoto
Yuichiro
Y
Shimokawa
Chizu
C
Fukuyama
Keiichi
K
Palmer
Graham
G
Noguchi
Masato
M
D000818:Animals; D018360:Crystallography, X-Ray / Q000379:methods*; D006418:Heme / Q000031:analogs & derivatives* / Q000737:chemistry; D051547:Heme Oxygenase-1 / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats
C099547:verdoheme; D006418:Heme; D051547:Heme Oxygenase-1