TY - JOUR
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
PY - 2004/5/14
Y1 - 2004/5/14
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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U2 - 10.1074/jbc.M400491200
DO - 10.1074/jbc.M400491200
M3 - Article
C2 - 14966119
AN - SCOPUS:2442645409
SN - 0021-9258
VL - 279
SP - 21055
EP - 21061
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 20
ER -