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U.S. Department of Health and Human Services

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J Biol Chem 2013 Feb 8;288(6):4288-98

Alpha-hemoglobin stabilizing protein (AHSP) markedly decreases the redox potential and reactivity of alpha subunits of human HbA with hydrogen peroxide.

Mollan TL, Banerjee S, Wu G, Parker Siburt CJ, Tsai AL, Olson JS, Weiss MJ, Crumbliss AL, Alayash AI


Alpha-Hemoglobin Stabilizing Protein (AHSP) is a molecular chaperone that binds monomeric alpha subunits of human hemoglobin A (HbA) and modulates heme iron oxidation and subunit folding states. Although AHSP:alphaHb complexes autooxidize more rapidly than HbA, the redox mechanisms appear to be similar. Both metHbA and isolated met-beta subunits undergo further oxidation in the presence of hydrogen peroxide (H2O2) to form ferryl heme species. Surprisingly, much lower levels of H2O2-induced ferryl iron are produced by free met-alpha subunits as compared to met-beta subunits, and no ferryl heme iron is detected in H2O2-treated AHSP:met-alpha complex at pH values from 5.0 to 9.0 at 23 OC. Ferryl heme species were similarly not detected in AHSP:met-alpha Pro30 mutants known to exhibit different rates of autooxidation and hemin loss. EPR data suggest that protein-based radicals associated with the ferryl oxidation state exist within HbA alpha and beta subunits. In contrast, treatment of free alpha subunits with H2O2 yields much smaller radical signals, and no radicals are detected when H2O2 is added to AHSP:alpha complexes. AHSP binding also dramatically reduces the redox potential of alpha subunits, from +40 mV to -78 mV in 1 M glycine buffer, pH 6.0 at 8 OC, demonstrating independently that AHSP has a much higher affinity for FeIII versus FeII alpha subunits. Hexacoordination in the AHSP:met-alpha complex markedly decreases the rate of the initial H2O2 reaction with iron and thus provides alpha subunits protection against damaging oxidative reactions.

Category: Journal Article
PubMed ID: #23264625 DOI: 10.1074/jbc.M112.412064
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2012-12-25 Entry Last Modified: 2013-04-23