Linked Life Data

12433915

Source:http://linkedlifedata.com/resource/pubmed/id/12433915

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-1-20
pubmed:abstractText
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 Fe(3+)-NO hHO-1-heme complex is formed with NO or the NO donors NOC9 or 2-(N,N-diethylamino)-diazenolate-2-oxide.sodium salt. Resonance Raman spectroscopy shows that ferric hHO-1-heme forms a 6-coordinated, low spin complex with NO. The nu(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 Fe(3+)-NO complex of hHO-1 is much more stable than that of met-Mb. Stopped-flow studies indicate that k(on) for formation of the hHO-1-heme Fe(3+)-NO complex is approximately 50-times faster, and k(off) 10 times slower, than for met-Mb, resulting in K(d) = 1.4 microm 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 K(d) 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2341-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12433915-Animals, pubmed-meshheading:12433915-Bilirubin, pubmed-meshheading:12433915-Cattle, pubmed-meshheading:12433915-Dose-Response Relationship, Drug, pubmed-meshheading:12433915-Heme, pubmed-meshheading:12433915-Heme Oxygenase (Decyclizing), pubmed-meshheading:12433915-Heme Oxygenase-1, pubmed-meshheading:12433915-Horses, pubmed-meshheading:12433915-Humans, pubmed-meshheading:12433915-Kinetics, pubmed-meshheading:12433915-Ligands, pubmed-meshheading:12433915-Membrane Proteins, pubmed-meshheading:12433915-Mutation, pubmed-meshheading:12433915-Nitric Oxide, pubmed-meshheading:12433915-Oxygen, pubmed-meshheading:12433915-Protein Binding, pubmed-meshheading:12433915-Protein Conformation, pubmed-meshheading:12433915-Spectrophotometry, pubmed-meshheading:12433915-Spectroscopy, Fourier Transform Infrared, pubmed-meshheading:12433915-Spectrum Analysis, Raman, pubmed-meshheading:12433915-Ultraviolet Rays
pubmed:year
2003
pubmed:articleTitle
Interaction of nitric oxide with human heme oxygenase-1.
pubmed:affiliation
Department of Pharmaceutical Chemistry, University of California, San Francisco, 94143-0446, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.