ArticleBiochemistry2015
Exploring the mechanisms of the reductase activity of neuroglobin by site-directed mutagenesis of the heme distal pocket.
Article in Biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 78 citations in OpenAlex.
- Effects of Oral Sodium Nitrite on Blood Pressure, Insulin Sensitivity, and Intima-Media Arterial Thickening in Adults With Hypertension and Metabolic Syndrome.Hypertension (Dallas, Tex. : 1979) · 2020Trial
- Immobilized neuroglobin scavenges carbon monoxide from circulating carboxyhemoglobin.bioRxiv : the preprint server for biology · 2026Article
- Artificial Oxygen Carriers: Lessons From Hemoglobin-Based Oxygen Carrier Clinical Trials and Current Development Efforts.Shock (Augusta, Ga.) · 2026Review
- Cytochrome bFree radical biology & medicine · 2026Article
- CytochromebioRxiv : the preprint server for biology · 2025Article
- Engineering a highly selective, hemoprotein-based scavenger as a carbon monoxide poisoning antidote with no hypertensive effect.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Nitrite Reductases in Biomedicine: From Natural Enzymes to Artificial Mimics.Research (Washington, D.C.) · 2025Review
- Hell's Gate Globin-I fromInternational journal of molecular sciences · 2024Article
- Facilitating Nitrite-Derived S-Nitrosothiol Formation in the Upper Gastrointestinal Tract in the Therapy of Cardiovascular Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Engineering neuroglobin nitrite reductase activity based on myoglobin models.Biochemistry and biophysics reports · 2023Article
- Peroxidase activity of rice (Oryza sativa) hemoglobin: distinct role of tyrosines 112 and 151.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2023Article
- Molecular Interactions between Neuroglobin and CytochromeBiomolecules · 2023Review
- Hydrogen peroxide induces heme degradation and protein aggregation in human neuroglobin: roles of the disulfide bridge and hydrogen-bonding in the distal heme cavity.The FEBS journal · 2023Article
- Modulating Nitric Oxide Dioxygenase and Nitrite Reductase of Cytoglobin through Point Mutations.Antioxidants (Basel, Switzerland) · 2022Article
- New Strategies for Stroke Therapy: Nanoencapsulated Neuroglobin.Pharmaceutics · 2022Review
- Regulation of nitrite reductase and lipid binding properties of cytoglobin by surface and distal histidine mutations.Nitric oxide : biology and chemistry · 2022Article
- Engineering globins for efficient biodegradation of malachite green: two case studies of myoglobin and neuroglobin.RSC advances · 2022Article
- The role of globins in cardiovascular physiology.Physiological reviews · 2022Review
- Structural and (Pseudo-)Enzymatic Properties of Neuroglobin: Its Possible Role in Neuroprotection.Cells · 2021Review
- Endogenous Hemoprotein-Dependent Signaling Pathways of Nitric Oxide and Nitrite.Inorganic chemistry · 2021Review
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Neuroglobin (Ngb) is a six-coordinate globin that can catalyze the reduction of nitrite to nitric oxide. Although this reaction is common to heme proteins, the molecular interactions in the heme pocket that regulate this reaction are largely unknown. We have shown that the H64L Ngb mutation increases the rate of nitrite reduction by 2000-fold compared to that of wild-type Ngb [Tiso, M., et al. (2011) J. Biol. Chem. 286, 18277-18289]. Here we explore the effect of distal heme pocket mutations on nitrite reduction. For this purpose, we have generated mutations of Ngb residues Phe28(B10), His64(E7), and Val68(E11). Our results indicate a dichotomy in the reactivity of deoxy five- and six-coordinate globins toward nitrite. In hemoglobin and myoglobin, there is a correlation between faster rates and more negative potentials. However, in Ngb, reaction rates are apparently related to the distal pocket volume, and redox potential shows a poor relationship with the rate constants. This suggests a relationship between the nitrite reduction rate and heme accessibility in Ngb, particularly marked for His64(E7) mutants. In five-coordinate globins, His(E7) facilitates nitrite reduction, likely through proton donation. Conversely, in Ngb, the reduction mechanism does not rely on the delivery of a proton from the histidine side chain, as His64 mutants show the fastest reduction rates. In fact, the rate observed for H64A Ngb (1120 M(-1) s(-1)) is to the best of our knowledge the fastest reported for a heme nitrite reductase. These differences may be related to a differential stabilization of the iron-nitrite complexes in five- and six-coordinate globins.
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