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Glutathione Non-covalent Binding Sites on Hemoglobin and Major Glutathionylation Target betaCys94 Are Conservative among Both Hypoxia-Sensitive and Hypoxia-Tolerant Mammal Species
Anashkina, A.A.; Simonenko, S.Y.; Orlov, Y.L.; Petrushanko, I.Y. Glutathione Non-Covalent Binding Sites on Hemoglobin and Major Glutathionylation Target betaCys93 Are Conservative among Both Hypoxia-Sensitive and Hypoxia-Tolerant Mammal Species. Int. J. Mol. Sci.2024, 25, 53.
Anashkina, A.A.; Simonenko, S.Y.; Orlov, Y.L.; Petrushanko, I.Y. Glutathione Non-Covalent Binding Sites on Hemoglobin and Major Glutathionylation Target betaCys93 Are Conservative among Both Hypoxia-Sensitive and Hypoxia-Tolerant Mammal Species. Int. J. Mol. Sci. 2024, 25, 53.
Anashkina, A.A.; Simonenko, S.Y.; Orlov, Y.L.; Petrushanko, I.Y. Glutathione Non-Covalent Binding Sites on Hemoglobin and Major Glutathionylation Target betaCys93 Are Conservative among Both Hypoxia-Sensitive and Hypoxia-Tolerant Mammal Species. Int. J. Mol. Sci.2024, 25, 53.
Anashkina, A.A.; Simonenko, S.Y.; Orlov, Y.L.; Petrushanko, I.Y. Glutathione Non-Covalent Binding Sites on Hemoglobin and Major Glutathionylation Target betaCys93 Are Conservative among Both Hypoxia-Sensitive and Hypoxia-Tolerant Mammal Species. Int. J. Mol. Sci. 2024, 25, 53.
Abstract
: Intracellular tripeptide glutathione is an important agent of cell survival in hypoxia. Glutathione covalently binds to SH-groups of hemoglobin cysteine residues, protecting them from irreversible oxidation and changes its affinity to oxygen. Reduced glutathione (GSH) can also form a non-covalent complex with hemoglobin. Previously, we showed that hemoglobin tetramer has four noncovalent binding sites of glutathione GSH molecules inside, two of which are released during hemoglobin transition to deoxy form. In this study, we characterized the conserved cysteine residues and residues of non-covalent glutathione binding sites in the sequences of a number of hypoxia tolerant and hypoxia-sensitive mammals. The alpha subunit of all species considered was found to have no conserved cysteines, whereas the beta subunit contains Cys94 residue, which is conserved across species and whose glutathionylation changes the affinity of hemoglobin for oxygen 5-6-fold. In addition, the key residues of noncovalent glutathione binding sites in both alpha and beta subunits are absolutely conserved in all species considered, suggesting a common mechanism of hemoglobin redox regulation for both hypoxia-sensitive and hypoxia-tolerant mammals. The solvent accessibility of all HbA and HbB residues in oxy- and deoxy- forms was analyzed. The key residue betaCys94 is solvent accessible only in the deoxy form.
Biology and Life Sciences, Biochemistry and Molecular Biology
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