ArticleThe Journal of biological chemistry2011
Structural and functional studies indicating altered redox properties of hemoglobin E: implications for production of bioactive nitric oxide.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- The Role of Cytochrome P450 Holoenzyme Metabolism in the Origin of Neuropathologies.International journal of molecular sciences · 2026Review
- Molecular Dynamics Reveals Unique Distal Histidine Positions and Interfacial Transitions of Fish and Mammalian Deoxyhemoglobin at Post-mortem pH.Journal of agricultural and food chemistry · 2025Article
- Hemoglobin Variants as Targets for Stabilizing Drugs.Molecules (Basel, Switzerland) · 2025Review
- Ultrasensitive electrochemical molecularly imprinted sensor based on AuE/Ag-MOF@MC for determination of hemoglobin using response surface methodology.Analytical and bioanalytical chemistry · 2021Article
- Decreased nitrite reductase activity of deoxyhemoglobin correlates with platelet activation in hemoglobin E/ß-thalassemia subjects.PloS one · 2018Article
- HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics.Antioxidants & redox signaling · 2017Review
- Oxidized Mutant Human Hemoglobins S and E Induce Oxidative Stress and Bioenergetic Dysfunction in Human Pulmonary Endothelial Cells.Frontiers in physiology · 2017Article
- Polyethylene Glycol Camouflaged Earthworm Hemoglobin.PloS one · 2017Article
- Article
- Evaluating the capacity to generate and preserve nitric oxide bioactivity in highly purified earthworm erythrocruorin: a giant polymeric hemoglobin with potential blood substitute properties.The Journal of biological chemistry · 2015Article
- The capacity of red blood cells to reduce nitrite determines nitric oxide generation under hypoxic conditions.PloS one · 2014Article
- Generating S-nitrosothiols from hemoglobin: mechanisms, conformational dependence, and physiological relevance.The Journal of biological chemistry · 2013Article
- HBOC vasoactivity: interplay between nitric oxide scavenging and capacity to generate bioactive nitric oxide species.Antioxidants & redox signaling · 2013Review
- Differential thermal stability and oxidative vulnerability of the hemoglobin variants, HbA2 and HbE.PloS one · 2013Article
- Enhanced nitrite reductase activity associated with the haptoglobin complexed hemoglobin dimer: functional and antioxidative implications.Nitric oxide : biology and chemistry · 2012Article
- A transgenic mouse model expressing exclusively human hemoglobin E: indications of a mild oxidative stress.Blood cells, molecules & diseases · 2012Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Hemoglobin (Hb) E (β-Glu26Lys) remains an enigma in terms of its contributions to red blood cell (RBC) pathophysiological mechanisms; for example, EE individuals exhibit a mild chronic anemia, and HbE/β-thalassemia individuals show a range of clinical manifestations, including high morbidity and death, often resulting from cardiac dysfunction. The purpose of this study was to determine and evaluate structural and functional consequences of the HbE mutation that might account for the pathophysiology. Functional studies indicate minimal allosteric consequence to both oxygen and carbon monoxide binding properties of the ferrous derivatives of HbE. In contrast, redox-sensitive reactions are clearly impacted as seen in the following: 1) the ∼2.5 times decrease in the rate at which HbE catalyzes nitrite reduction to nitric oxide (NO) relative to HbA, and 2) the accelerated rate of reduction of aquometHbE by L-cysteine (L-Cys). Sol-gel encapsulation studies imply a shift toward a higher redox potential for both the T and R HbE structures that can explain the origin of the reduced nitrite reductase activity of deoxyHbE and the accelerated rate of reduction of aquometHbE by cysteine. Deoxy- and CO HbE crystal structures (derived from crystals grown at or near physiological pH) show loss of hydrogen bonds in the microenvironment of βLys-26 and no significant tertiary conformational perturbations at the allosteric transition sites in the R and T states. Together, these data suggest a model in which the HbE mutation, as a consequence of a relative change in redox properties, decreases the overall rate of Hb-mediated production of bioactive NO.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.