Crystal structure of the dioxygen-bound heme oxygenase from Corynebacterium diphtheriae: Implications for heme oxygenase function

Masaki Unno, Toshitaka Matsui, Grace C. Chu, Manon Couture, Tadashi Yoshida, Denis L. Rousseau, John S. Olson, Masao Ikeda-Saito

Research output: Contribution to journalArticle

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Abstract

HmuO, a heme oxygenase of Corynebacterium diphtheriae, catalyzes degradation of heme using the same mechanism as the mammalian enzyme. The oxy form of HmuO, the precursor of the catalytically active ferric hydroperoxo species, has been characterized by ligand binding kinetics, resonance Raman spectroscopy, and x-ray crystallography. The oxygen association and dissociation rate constants are 5 μM-1 s-1 and 0.22 s-1, respectively, yielding an O2 affinity of 21 μM-1, which is ∼20 times greater than that of mammalian myoglobins. However, the affinity of HmuO for CO is only 3-4-fold greater than that for mammalian myoglobins, implying the presence of strong hydrogen bonding interactions in the distal pocket of HmuO that preferentially favor O 2 binding. Resonance Raman spectra show that the Fe-O2 vibrations are tightly coupled to porphyrin vibrations, indicating the highly bent Fe-O-O geometry that is characteristic of the oxy forms of heme oxygenases. In the crystal structure of the oxy form the Fe-O-O angle is 110°, the O-O bond is pointed toward the heme α-meso-carbon by direct steric interactions with Gly-135 and Gly-139, and hydrogen bonds occur between the bound O2 and the amide nitrogen of Gly-139 and a distal pocket water molecule, which is a part of an extended hydrogen bonding network that provides the solvent protons required for oxygen activation. In addition, the O-O bond is orthogonal to the plane of the proximal imidazole side chain, which facilitates hydroxylation of the porphyrin α-nteso-carbon by preventing premature O-O bond cleavage.

Original languageEnglish (US)
Pages (from-to)21055-21061
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number20
DOIs
StatePublished - May 14 2004

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Corynebacterium diphtheriae
Heme Oxygenase (Decyclizing)
Myoglobin
Porphyrins
Hydrogen Bonding
Vibration
Heme
Hydrogen bonds
Carbon
Crystal structure
Oxygen
Crystallography
Raman Spectrum Analysis
Carbon Monoxide
Hydroxylation
Amides
Protons
Hydrogen
Nitrogen
X-Rays

ASJC Scopus subject areas

  • Biochemistry

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Crystal structure of the dioxygen-bound heme oxygenase from Corynebacterium diphtheriae : Implications for heme oxygenase function. / Unno, Masaki; Matsui, Toshitaka; Chu, Grace C.; Couture, Manon; Yoshida, Tadashi; Rousseau, Denis L.; Olson, John S.; Ikeda-Saito, Masao.

In: Journal of Biological Chemistry, Vol. 279, No. 20, 14.05.2004, p. 21055-21061.

Research output: Contribution to journalArticle

Unno, Masaki ; Matsui, Toshitaka ; Chu, Grace C. ; Couture, Manon ; Yoshida, Tadashi ; Rousseau, Denis L. ; Olson, John S. ; Ikeda-Saito, Masao. / Crystal structure of the dioxygen-bound heme oxygenase from Corynebacterium diphtheriae : Implications for heme oxygenase function. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 20. pp. 21055-21061.
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abstract = "HmuO, a heme oxygenase of Corynebacterium diphtheriae, catalyzes degradation of heme using the same mechanism as the mammalian enzyme. The oxy form of HmuO, the precursor of the catalytically active ferric hydroperoxo species, has been characterized by ligand binding kinetics, resonance Raman spectroscopy, and x-ray crystallography. The oxygen association and dissociation rate constants are 5 μM-1 s-1 and 0.22 s-1, respectively, yielding an O2 affinity of 21 μM-1, which is ∼20 times greater than that of mammalian myoglobins. However, the affinity of HmuO for CO is only 3-4-fold greater than that for mammalian myoglobins, implying the presence of strong hydrogen bonding interactions in the distal pocket of HmuO that preferentially favor O 2 binding. Resonance Raman spectra show that the Fe-O2 vibrations are tightly coupled to porphyrin vibrations, indicating the highly bent Fe-O-O geometry that is characteristic of the oxy forms of heme oxygenases. In the crystal structure of the oxy form the Fe-O-O angle is 110°, the O-O bond is pointed toward the heme α-meso-carbon by direct steric interactions with Gly-135 and Gly-139, and hydrogen bonds occur between the bound O2 and the amide nitrogen of Gly-139 and a distal pocket water molecule, which is a part of an extended hydrogen bonding network that provides the solvent protons required for oxygen activation. In addition, the O-O bond is orthogonal to the plane of the proximal imidazole side chain, which facilitates hydroxylation of the porphyrin α-nteso-carbon by preventing premature O-O bond cleavage.",
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T1 - Crystal structure of the dioxygen-bound heme oxygenase from Corynebacterium diphtheriae

T2 - Implications for heme oxygenase function

AU - Unno, Masaki

AU - Matsui, Toshitaka

AU - Chu, Grace C.

AU - Couture, Manon

AU - Yoshida, Tadashi

AU - Rousseau, Denis L.

AU - Olson, John S.

AU - Ikeda-Saito, Masao

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N2 - HmuO, a heme oxygenase of Corynebacterium diphtheriae, catalyzes degradation of heme using the same mechanism as the mammalian enzyme. The oxy form of HmuO, the precursor of the catalytically active ferric hydroperoxo species, has been characterized by ligand binding kinetics, resonance Raman spectroscopy, and x-ray crystallography. The oxygen association and dissociation rate constants are 5 μM-1 s-1 and 0.22 s-1, respectively, yielding an O2 affinity of 21 μM-1, which is ∼20 times greater than that of mammalian myoglobins. However, the affinity of HmuO for CO is only 3-4-fold greater than that for mammalian myoglobins, implying the presence of strong hydrogen bonding interactions in the distal pocket of HmuO that preferentially favor O 2 binding. Resonance Raman spectra show that the Fe-O2 vibrations are tightly coupled to porphyrin vibrations, indicating the highly bent Fe-O-O geometry that is characteristic of the oxy forms of heme oxygenases. In the crystal structure of the oxy form the Fe-O-O angle is 110°, the O-O bond is pointed toward the heme α-meso-carbon by direct steric interactions with Gly-135 and Gly-139, and hydrogen bonds occur between the bound O2 and the amide nitrogen of Gly-139 and a distal pocket water molecule, which is a part of an extended hydrogen bonding network that provides the solvent protons required for oxygen activation. In addition, the O-O bond is orthogonal to the plane of the proximal imidazole side chain, which facilitates hydroxylation of the porphyrin α-nteso-carbon by preventing premature O-O bond cleavage.

AB - HmuO, a heme oxygenase of Corynebacterium diphtheriae, catalyzes degradation of heme using the same mechanism as the mammalian enzyme. The oxy form of HmuO, the precursor of the catalytically active ferric hydroperoxo species, has been characterized by ligand binding kinetics, resonance Raman spectroscopy, and x-ray crystallography. The oxygen association and dissociation rate constants are 5 μM-1 s-1 and 0.22 s-1, respectively, yielding an O2 affinity of 21 μM-1, which is ∼20 times greater than that of mammalian myoglobins. However, the affinity of HmuO for CO is only 3-4-fold greater than that for mammalian myoglobins, implying the presence of strong hydrogen bonding interactions in the distal pocket of HmuO that preferentially favor O 2 binding. Resonance Raman spectra show that the Fe-O2 vibrations are tightly coupled to porphyrin vibrations, indicating the highly bent Fe-O-O geometry that is characteristic of the oxy forms of heme oxygenases. In the crystal structure of the oxy form the Fe-O-O angle is 110°, the O-O bond is pointed toward the heme α-meso-carbon by direct steric interactions with Gly-135 and Gly-139, and hydrogen bonds occur between the bound O2 and the amide nitrogen of Gly-139 and a distal pocket water molecule, which is a part of an extended hydrogen bonding network that provides the solvent protons required for oxygen activation. In addition, the O-O bond is orthogonal to the plane of the proximal imidazole side chain, which facilitates hydroxylation of the porphyrin α-nteso-carbon by preventing premature O-O bond cleavage.

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