Replacement of the distal glycine 139 transforms human heme oxygenase-1 into a peroxidase

Yi Liu, Luke Koenigs Lightning, Hong Wei Huang, Pierre Moënne-Loccoz, David J. Schuller, Thomas L. Poulos, Thomas M. Loehr, Paul R. Ortiz De Montellano

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


The human heine oxygenase-1 crystal structure suggests that Gly-139 and Gly-143 interact directly with iron-bound ligands. We have mutated Gly-139 to an alanine, leucine, phenylalanine, tryptophan, histidine, or aspartate, and Gly-143 to a leucine, lysine, histidine, or aspartate. All of these mutants bind heine, but absorption and resonance Raman spectroscopy indicate that the water coordinated to the iron atom is lost in several of the Gly-139 mutants, giving rise to mixtures of hexacoordinate and pentacoordinate ligation states. The active site perturbation is greatest when large amino acid side chains are introduced. Of the Gly-139 mutants investigated, only G139A catalyzes the NADPH-cytochrome P450 reductase-dependent oxidation of heme to biliverdin, but most of them exhibit a new H2O2-dependent guaiacol peroxidation activity. The Gly-143 mutants, all of which have lost the water ligand, have no heme oxygenase or peroxidase activity. The results establish the importance of Gly-139 and Gly-143 in maintaining the appropriate environment for the heme oxygenase reaction and show that Gly-139 mutations disrupt this environment, probably by displacing the distal helix, converting heme oxygenase into a peroxidase. The principal role of the heme oxygenase active site may be to suppress the ferryl species formation responsible for peroxidase activity.

Original languageEnglish (US)
Pages (from-to)34501-34507
Number of pages7
JournalJournal of Biological Chemistry
Issue number44
StatePublished - Nov 3 2000

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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