Crystal structure of human heme oxygenase-1 in a complex with biliverdin.
Heme oxygenase oxidatively cleaves heme to biliverdin, leading to the release of iron and CO through a process in which the heme participates both as a cofactor and as a substrate. Here we report the crystal structure of the product, iron-free biliverdin, in a complex with human HO-1 at 2.19 A. Structural comparisons of the human biliverdin-HO-1 structure with its heme complex and the recently published rat HO-1 structure in a complex with the biliverdin-iron chelate [Sugishima, M., Sakamoto, H., Higashimoto, Y., Noguchi, M., and Fukuyama, K. (2003) J. Biol. Chem. 278, 32352-32358] show two major differences. First, in the absence of an Fe-His bond and solvent structure in the active site, the distal and proximal helices relax and adopt an "open" conformation which most likely encourages biliverdin release. Second, iron-free biliverdin occupies a different position and orientation relative to heme and the biliverdin-iron complex. Biliverdin adopts a more linear conformation and moves from the heme site to an internal cavity. These structural results provide insight into the rate-limiting step in HO-1 catalysis, which is product, biliverdin, release.
Lad
Latesh
L
Department of Molecular Biology and Biochemistry, Program in Macromolecular Structure, University of California, Irvine, California 92697-3900, USA.
Friedman
Jonathan
J
Li
Huying
H
Bhaskar
B
B
Ortiz de Montellano
Paul R
PR
Poulos
Thomas L
TL
D000818:Animals; D001664:Biliverdine / Q000737:chemistry*; D001665:Binding Sites; D002384:Catalysis; D003198:Computer Simulation; D003460:Crystallization; D018360:Crystallography, X-Ray; D005290:Ferric Compounds / Q000737:chemistry; D006418:Heme / Q000737:chemistry; D006419:Heme Oxygenase (Decyclizing) / Q000737:chemistry*; D051547:Heme Oxygenase-1; D006801:Humans; D046911:Macromolecular Substances; D008565:Membrane Proteins; D008958:Models, Molecular; D011485:Protein Binding; D017433:Protein Structure, Secondary; D051381:Rats
D005290:Ferric Compounds; D046911:Macromolecular Substances; D008565:Membrane Proteins; D006418:Heme; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001664:Biliverdine