Interaction of nitric oxide with human heme oxygenase-1

Jinling Wang, Shen Lu, Pierre Moenne-Loccoz, Paul R. Ortiz de Montellano

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

NO and CO may complement each other as signaling molecules in some physiological situations. We have examined the binding of NO to human heme oxygenase-1 (hHO-1), an enzyme that oxidizes heme to biliverdin, CO, and free iron, to determine whether inhibition of hHO-1 by NO can contribute to the signaling interplay of NO and CO. An Fe3+-NO hHO-1-heme complex is formed with NO or the NO donors NOC9 or 2-(N,N-diethyl-amino)-diazenolate-2-oxide·sodium salt. Resonance Raman spectroscopy shows that ferric hHO-1-heme forms a 6-coordinated, low spin complex with NO. The v(N-O) vibration of this complex detected by Fourier transform IR is only 4 cm-1 lower than that of the corresponding metmyoglobin (met-Mb) complex but is broader, suggesting a greater degree of ligand conformational freedom. The Fe3+-NO complex of hHO-1 is much more stable than that of met-Mb. Stopped-flow studies indicate that kon for formation of the hHO-1-heme Fe3+-NO complex is ∼50-times faster, and koff 10 times slower, than for met-Mb, resulting in Kd = 1.4 μM for NO. NO thus binds 500-fold more tightly to ferric hHO-1-heme than to met-Mb. The hHO-1 mutations E29A, G139A, D140A, S142A, G143A, G143F, and K179A/R183A do not significantly diminish the tight binding of NO, indicating that NO binding is not highly sensitive to mutations of residues that normally stabilize the distal water ligand. As expected from the Kd value, the enzyme is reversibly inhibited upon exposure to pathologically, and possibly physiologically, relevant concentrations of NO. Inhibition of hHO-1 by NO may contribute to the pleiotropic responses to NO and CO.

Original languageEnglish (US)
Pages (from-to)2341-2347
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number4
DOIs
StatePublished - Jan 24 2003

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Heme Oxygenase-1
Nitric Oxide
Heme
Carbon Monoxide
Metmyoglobin
Biliverdine
Ligands
Mutation
Raman Spectrum Analysis
Fourier Analysis
Enzymes
Vibration
Raman spectroscopy
Fourier transforms
Iron
Salts
Molecules
Water

ASJC Scopus subject areas

  • Biochemistry

Cite this

Interaction of nitric oxide with human heme oxygenase-1. / Wang, Jinling; Lu, Shen; Moenne-Loccoz, Pierre; Ortiz de Montellano, Paul R.

In: Journal of Biological Chemistry, Vol. 278, No. 4, 24.01.2003, p. 2341-2347.

Research output: Contribution to journalArticle

Wang, Jinling ; Lu, Shen ; Moenne-Loccoz, Pierre ; Ortiz de Montellano, Paul R. / Interaction of nitric oxide with human heme oxygenase-1. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 4. pp. 2341-2347.
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abstract = "NO and CO may complement each other as signaling molecules in some physiological situations. We have examined the binding of NO to human heme oxygenase-1 (hHO-1), an enzyme that oxidizes heme to biliverdin, CO, and free iron, to determine whether inhibition of hHO-1 by NO can contribute to the signaling interplay of NO and CO. An Fe3+-NO hHO-1-heme complex is formed with NO or the NO donors NOC9 or 2-(N,N-diethyl-amino)-diazenolate-2-oxide·sodium salt. Resonance Raman spectroscopy shows that ferric hHO-1-heme forms a 6-coordinated, low spin complex with NO. The v(N-O) vibration of this complex detected by Fourier transform IR is only 4 cm-1 lower than that of the corresponding metmyoglobin (met-Mb) complex but is broader, suggesting a greater degree of ligand conformational freedom. The Fe3+-NO complex of hHO-1 is much more stable than that of met-Mb. Stopped-flow studies indicate that kon for formation of the hHO-1-heme Fe3+-NO complex is ∼50-times faster, and koff 10 times slower, than for met-Mb, resulting in Kd = 1.4 μM for NO. NO thus binds 500-fold more tightly to ferric hHO-1-heme than to met-Mb. The hHO-1 mutations E29A, G139A, D140A, S142A, G143A, G143F, and K179A/R183A do not significantly diminish the tight binding of NO, indicating that NO binding is not highly sensitive to mutations of residues that normally stabilize the distal water ligand. As expected from the Kd value, the enzyme is reversibly inhibited upon exposure to pathologically, and possibly physiologically, relevant concentrations of NO. Inhibition of hHO-1 by NO may contribute to the pleiotropic responses to NO and CO.",
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N2 - NO and CO may complement each other as signaling molecules in some physiological situations. We have examined the binding of NO to human heme oxygenase-1 (hHO-1), an enzyme that oxidizes heme to biliverdin, CO, and free iron, to determine whether inhibition of hHO-1 by NO can contribute to the signaling interplay of NO and CO. An Fe3+-NO hHO-1-heme complex is formed with NO or the NO donors NOC9 or 2-(N,N-diethyl-amino)-diazenolate-2-oxide·sodium salt. Resonance Raman spectroscopy shows that ferric hHO-1-heme forms a 6-coordinated, low spin complex with NO. The v(N-O) vibration of this complex detected by Fourier transform IR is only 4 cm-1 lower than that of the corresponding metmyoglobin (met-Mb) complex but is broader, suggesting a greater degree of ligand conformational freedom. The Fe3+-NO complex of hHO-1 is much more stable than that of met-Mb. Stopped-flow studies indicate that kon for formation of the hHO-1-heme Fe3+-NO complex is ∼50-times faster, and koff 10 times slower, than for met-Mb, resulting in Kd = 1.4 μM for NO. NO thus binds 500-fold more tightly to ferric hHO-1-heme than to met-Mb. The hHO-1 mutations E29A, G139A, D140A, S142A, G143A, G143F, and K179A/R183A do not significantly diminish the tight binding of NO, indicating that NO binding is not highly sensitive to mutations of residues that normally stabilize the distal water ligand. As expected from the Kd value, the enzyme is reversibly inhibited upon exposure to pathologically, and possibly physiologically, relevant concentrations of NO. Inhibition of hHO-1 by NO may contribute to the pleiotropic responses to NO and CO.

AB - NO and CO may complement each other as signaling molecules in some physiological situations. We have examined the binding of NO to human heme oxygenase-1 (hHO-1), an enzyme that oxidizes heme to biliverdin, CO, and free iron, to determine whether inhibition of hHO-1 by NO can contribute to the signaling interplay of NO and CO. An Fe3+-NO hHO-1-heme complex is formed with NO or the NO donors NOC9 or 2-(N,N-diethyl-amino)-diazenolate-2-oxide·sodium salt. Resonance Raman spectroscopy shows that ferric hHO-1-heme forms a 6-coordinated, low spin complex with NO. The v(N-O) vibration of this complex detected by Fourier transform IR is only 4 cm-1 lower than that of the corresponding metmyoglobin (met-Mb) complex but is broader, suggesting a greater degree of ligand conformational freedom. The Fe3+-NO complex of hHO-1 is much more stable than that of met-Mb. Stopped-flow studies indicate that kon for formation of the hHO-1-heme Fe3+-NO complex is ∼50-times faster, and koff 10 times slower, than for met-Mb, resulting in Kd = 1.4 μM for NO. NO thus binds 500-fold more tightly to ferric hHO-1-heme than to met-Mb. The hHO-1 mutations E29A, G139A, D140A, S142A, G143A, G143F, and K179A/R183A do not significantly diminish the tight binding of NO, indicating that NO binding is not highly sensitive to mutations of residues that normally stabilize the distal water ligand. As expected from the Kd value, the enzyme is reversibly inhibited upon exposure to pathologically, and possibly physiologically, relevant concentrations of NO. Inhibition of hHO-1 by NO may contribute to the pleiotropic responses to NO and CO.

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