ArticleThe Journal of biological chemistry2014
Post-translational transformation of methionine to aspartate is catalyzed by heme iron and driven by peroxide: a novel subunit-specific mechanism in hemoglobin.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 30 citations in OpenAlex.
- Case report: Curing a rare, unstable hemoglobin variant Hb Bristol-Alesha using haploidentical hematopoietic stem cell transplantation.Frontiers in immunology · 2023Article
- Oxidation of Hemoglobin Drives a Proatherogenic Polarization of Macrophages in Human Atherosclerosis.Antioxidants & redox signaling · 2021Article
- [Hb Alesha of unstable hemoglobinopathy: a case report and literature review].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2021Review
- The Providence Mutation (βK82D) in Human Hemoglobin Substantially Reduces βCysteine 93 Oxidation and Oxidative Stress in Endothelial Cells.International journal of molecular sciences · 2020Article
- Substitutions in the β subunits of sickle-cell hemoglobin improve oxidative stability and increase the delay time of sickle-cell fiber formation.The Journal of biological chemistry · 2019Article
- Antisickling Drugs Targeting βCys93 Reduce Iron Oxidation and Oxidative Changes in Sickle Cell Hemoglobin.Frontiers in physiology · 2019Article
- Hemoglobin oxidation-dependent reactions promote interactions with band 3 and oxidative changes in sickle cell-derived microparticles.JCI insight · 2018Article
- Site-directed mutagenesis of cysteine residues alters oxidative stability of fetal hemoglobin.Redox biology · 2018Article
- The change of synovial fluid proteome in rabbit surgery-induced model of knee osteoarthritis.American journal of translational research · 2018Article
- Targeting βCys93 in hemoglobin S with an antisickling agent possessing dual allosteric and antioxidant effects.Metallomics : integrated biometal science · 2017Article
- Exploring Oxidative Reactions in Hemoglobin Variants Using Mass Spectrometry: Lessons for Engineering Oxidatively Stable Oxygen Therapeutics.Antioxidants & redox signaling · 2017Review
- Determination of extinction coefficients of human hemoglobin in various redox states.Analytical biochemistry · 2017Article
- Article
- Evaluation of Stem Cell-Derived Red Blood Cells as a Transfusion Product Using a Novel Animal Model.PloS one · 2016Article
- Sickle Cell Hemoglobin in the Ferryl State Promotes βCys-93 Oxidation and Mitochondrial Dysfunction in Epithelial Lung Cells (E10).The Journal of biological chemistry · 2015Article
- Haptoglobin attenuates hemoglobin-induced heme oxygenase-1 in renal proximal tubule cells and kidneys of a mouse model of sickle cell disease.Blood cells, molecules & diseases · 2015Article
- Dissection of the radical reactions linked to fetal hemoglobin reveals enhanced pseudoperoxidase activity.Frontiers in physiology · 2015Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
A pathogenic V67M mutation occurs at the E11 helical position within the heme pockets of variant human fetal and adult hemoglobins (Hb). Subsequent post-translational modification of Met to Asp was reported in γ subunits of human fetal Hb Toms River (γ67(E11)Val → Met) and β subunits of adult Hb (HbA) Bristol-Alesha (β67(E11)Val → Met) that were associated with hemolytic anemia. Using kinetic, proteomic, and crystal structural analysis, we were able to show that the Met → Asp transformation involves heme cycling through its oxoferryl state in the recombinant versions of both proteins. The conversion to Met and Asp enhanced the spontaneous autoxidation of the mutants relative to wild-type HbA and human fetal Hb, and the levels of Asp were elevated with increasing levels of hydrogen peroxide (H2O2). Using H2(18)O2, we verified incorporation of (18)O into the Asp carboxyl side chain confirming the role of H2O2 in the oxidation of the Met side chain. Under similar experimental conditions, there was no conversion to Asp at the αMet(E11) position in the corresponding HbA Evans (α62(E11)Val → Met). The crystal structures of the three recombinant Met(E11) mutants revealed similar thioether side chain orientations. However, as in the solution experiments, autoxidation of the Hb mutant crystals leads to electron density maps indicative of Asp(E11) formation in β subunits but not in α subunits. This novel post-translational modification highlights the nonequivalence of human Hb α, β, and γ subunits with respect to redox reactivity and may have direct implications to α/β hemoglobinopathies and design of oxidatively stable Hb-based oxygen therapeutics.
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