Heme-heme oxygenase complex: Structure of the catalytic site and its implication for oxygen activation

Satoshi Takahashi, Jianling Wang, Denis L. Rousseau, Kazunobu Ishikawa, Tadashi Yoshida, Janette R. Host, Masao Ikeda-Saito

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

Heme oxygenase, a central monooxygenase enzyme of the heme catabolism and the associated generation of carbon monoxide, forms a 1:1 stoichiometric complex with iron protoporphyrin IX, which is a prosthetic active center and at the same time the substrate of the enzyme. By using EPR, resonance Raman, and optical absorption spectroscopic techniques, we have determined the axial ligand coordination of the enzyme-heme complex. The ferric heme iron in the heme-enzyme complex at neutral pH is six-coordinate high spin, while at alkaline pH (pKa 7.6), the complex becomes low spin. Spectra of ferrous forms of the complex indicate that histidine serves as the iron proximal axial ligand and that the residue is in its neutral imidazole rather than its imidazolate protonation state. Thus, the active site of the heme-heme oxygenase complex has a myoglobin-like structure rather than an active site similar to the large cytochrome P-450 class of monooxygenases. As a consequence, the activated form of the heme-heme oxygenase complex, a peroxo intermediate, is different from that of the cytochrome P-450 monooxygenases, in which the activated form is an oxo intermediate. The overall catalytic mechanism is probably more closely related to that of other monooxygenases with myoglobin-like active sites, such as secondary amine monooxygenase.

Original languageEnglish (US)
Pages (from-to)1010-1014
Number of pages5
JournalJournal of Biological Chemistry
Volume269
Issue number2
StatePublished - Jan 14 1994
Externally publishedYes

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Heme Oxygenase (Decyclizing)
Heme
Catalytic Domain
Chemical activation
Oxygen
Mixed Function Oxygenases
Myoglobin
Enzymes
Cytochrome P-450 Enzyme System
Iron
Ligands
Protonation
Carbon Monoxide
Prosthetics
Histidine
Light absorption
Paramagnetic resonance
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

Takahashi, S., Wang, J., Rousseau, D. L., Ishikawa, K., Yoshida, T., Host, J. R., & Ikeda-Saito, M. (1994). Heme-heme oxygenase complex: Structure of the catalytic site and its implication for oxygen activation. Journal of Biological Chemistry, 269(2), 1010-1014.

Heme-heme oxygenase complex : Structure of the catalytic site and its implication for oxygen activation. / Takahashi, Satoshi; Wang, Jianling; Rousseau, Denis L.; Ishikawa, Kazunobu; Yoshida, Tadashi; Host, Janette R.; Ikeda-Saito, Masao.

In: Journal of Biological Chemistry, Vol. 269, No. 2, 14.01.1994, p. 1010-1014.

Research output: Contribution to journalArticle

Takahashi, S, Wang, J, Rousseau, DL, Ishikawa, K, Yoshida, T, Host, JR & Ikeda-Saito, M 1994, 'Heme-heme oxygenase complex: Structure of the catalytic site and its implication for oxygen activation', Journal of Biological Chemistry, vol. 269, no. 2, pp. 1010-1014.
Takahashi, Satoshi ; Wang, Jianling ; Rousseau, Denis L. ; Ishikawa, Kazunobu ; Yoshida, Tadashi ; Host, Janette R. ; Ikeda-Saito, Masao. / Heme-heme oxygenase complex : Structure of the catalytic site and its implication for oxygen activation. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 2. pp. 1010-1014.
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