1XK0

Crystal Structures of the G139A, G139A-NO and G143H Mutants of Human Heme Oxygenase-1

Summary for 1XK0

• Entry DOI: 10.2210/pdb1xk0/pdb
• Related: 1XJZ 1XK1 1XK2 1XK3
• Descriptor: Heme oxygenase 1, PROTOPORPHYRIN IX CONTAINING FE, NITRIC OXIDE, ... (4 entities in total)
• Functional Keywords: heme, heme degredation, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Microsome: P09601
• Total number of polymer chains: 2
• Total formula weight: 55032.10

Authors

Lad, L.,Koshkin, A.,Ortiz de Montellano, P.R.,Poulos, T.L. (deposition date: 2004-09-26, release date: 2005-12-06, Last modification date: 2024-02-14)

Primary citation

Lad, L.,Koshkin, A.,Ortiz de Montellano, P.R.,Poulos, T.L.
Crystal structures of the G139A, G139A-NO and G143H mutants of human heme oxygenase-1. A finely tuned hydrogen-bonding network controls oxygenase versus peroxidase activity.
J.Biol.Inorg.Chem., 10:138-146, 2005

PubMed Abstract: Conserved glycines, Gly139 and Gly143, in the distal helix of human heme oxygenase-1 (HO-1) provide the flexibility required for the opening and closing of the heme active site for substrate binding and product dissociation during HO-1 catalysis. Earlier mutagenesis work on human HO-1 showed that replacement of either Gly139 or Gly143 suppresses heme oxygenase activity and, in the case of the Gly139 mutants, increases peroxidase activity (Liu et al. in J. Biol. Chem. 275:34501, 2000). To further investigate the role of the conserved distal helix glycines, we have determined the crystal structures of the human HO-1 G139A mutant, the G139A mutant in a complex with NO, and the G143H mutant at 1.88, 2.18 and 2.08 A, respectively. The results confirm that fine tuning of the previously noted active-site hydrogen-bonding network is critical in determining whether heme oxygenase or peroxidase activity is observed.

PubMed: 15690204
DOI: 10.1007/s00775-004-0620-6

Experimental method

X-RAY DIFFRACTION (2.18 Å)