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| | {{STRUCTURE_1tes| PDB=1tes | SCENE= }} | | {{STRUCTURE_1tes| PDB=1tes | SCENE= }} |
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| - | '''OXYGEN BINDING MUSCLE PROTEIN'''
| + | ===OXYGEN BINDING MUSCLE PROTEIN=== |
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| - | ==Overview==
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| - | Nitric oxide (NO) has been implicated as mediator in a variety of physiological functions, including neurotransmission, platelet aggregation, macrophage function, and vasodilation. The consumption of NO by extracellular hemoglobin and subsequent vasoconstriction have been suggested to be the cause of the mild hypertensive events reported during in vivo trials of hemoglobin-based O2 carriers. The depletion of NO from endothelial cells is most likely due to the oxidative reaction of NO with oxyhemoglobin in arterioles and surrounding tissue. In order to determine the mechanism of this key reaction, we have measured the kinetics of NO-induced oxidation of a variety of different recombinant sperm whale myoglobins (Mb) and human hemoglobins (Hb). The observed rates depend linearly on [NO] but show no dependence on [O2]. The bimolecular rate constants for NO-induced oxidation of MbO2 and HbO2 are large (k.ox,NO = 30-50 microM-1 s-1 for the wild-type proteins) and similar to those for simple nitric oxide binding to deoxygenated Mb and Hb. Both reversible NO binding and NO-induced oxidation occur in two steps: (1) bimolecular entry of nitric oxide into the distal portion of the heme pocket and (2) rapid reaction of noncovalently bound nitric oxide with the iron atom to produce Fe(2+)-N=O or with Fe(2+)-O-O delta- to produce Fe(3+)-OH2 and nitrate. Both the oxidation and binding rate constants for sperm whale Mb were increased when His(E7) was replaced by aliphatic residues. These mutants lack polar interactions in the distal pocket which normally hinder NO entry into the protein. Decreasing the volume of the distal pocket by replacing Leu(B10) and Val(E11) with aromatic amino acids markedly inhibits NO-induced oxidation of MbO2. The latter results provide a protein engineering strategy for reducing hypertensive events caused by extracellular hemoglobin-based O2 carriers. This approach has been explored by examining the effects of Phe(B10) and Phe(E11) substitutions on the rates of NO-induced oxidation of the alpha and beta subunits in recombinant human hemoglobin.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_8679521}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 8679521 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_8679521}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Olson, J S.]] | | [[Category: Olson, J S.]] |
| | [[Category: Smith, R D.]] | | [[Category: Smith, R D.]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 09:51:51 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 14:40:30 2008'' |
Revision as of 11:40, 28 July 2008
Template:STRUCTURE 1tes
OXYGEN BINDING MUSCLE PROTEIN
Template:ABSTRACT PUBMED 8679521
About this Structure
1TES is a Single protein structure of sequence from Physeter catodon. Full crystallographic information is available from OCA.
Reference
Mechanism of NO-induced oxidation of myoglobin and hemoglobin., Eich RF, Li T, Lemon DD, Doherty DH, Curry SR, Aitken JF, Mathews AJ, Johnson KA, Smith RD, Phillips GN Jr, Olson JS, Biochemistry. 1996 Jun 4;35(22):6976-83. PMID:8679521
Page seeded by OCA on Mon Jul 28 14:40:30 2008
