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Non-covalent and covalent modifications modulate the reactivity of monomeric mammalian globins

Ascenzi, Paolo and Marino, Maria and Polticelli, Fabio and Coletta, Massimo and Gioia, Magda and Marini, Stefano and Pesce, Alessandra and Nardini, Marco and Bolognesi, Martino and Reeder, Brandon J and Wilson, Michael T (2013) 'Non-covalent and covalent modifications modulate the reactivity of monomeric mammalian globins.' Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 1834 (9). pp. 1750-1756. ISSN 1570-9639

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Multimeric globins (e.g., hemoglobin) are considered to be the prototypes of allosteric enzymes, whereas monomeric globins (e.g., myoglobin; Mb) usually are assumed to be non-allosteric. However, the modulation of the functional properties of monomeric globins by non-covalent (or allosteric) and covalent modifications casts doubts on this general assumption. Here, we report examples referable to these two extreme mechanisms modulating the reactivity of three mammalian monomeric globins. Sperm whale Mb, which acts as a reserve supply of O2 and facilitates the O2 flux within a myocyte, displays the allosteric modulation of the O2 affinity on lactate, an obligatory product of glycolysis under anaerobic conditions, thus facilitating O2 diffusion to the mitochondria in supporting oxidative phosphorylation. Human neuroglobin (NGB), which appears to protect neurons from hypoxia in vitro and in vivo, undergoes hypoxia-dependent phosphorylation (i.e., covalent modulation) affecting the coordination equilibrium of the heme-Fe atom and, inturn, the heme-protein reactivity. This facilitates heme-Fe-ligand binding and enhances the rate of anaerobic nitrite reduction to form NO, thus contributing to cellular adaptation tohypoxia. The reactivity of human cytoglobin (CYGB), which has been postulated to protect cells against oxidative stress, depends on both non-covalent and covalent mechanisms. In fact, the heme reactivity of CYGB depends onthe lipid, suchasoleate, binding which stabilizes the penta-coordination geometry of the heme-Fe atom. Lastly, the reactivity of NGB and CYG Bismodulated by the redox state of the intramolecular CysCD7/CysD5 and CysB2/CysE9 residue pairs, respectively, affecting the heme-Fe atom coordination state. In conclusion, the modulation of monomeric globins reactivity by non-covalent and covalent modifications appears a very widespread phenomenon, opening new perspectivesincell survival and protection. This article ispart of a Special Issue entitled: Oxygen Binding and Sensing Proteins. © 2013 Elsevier B.V. All rights reserved.

Item Type: Article
Uncontrolled Keywords: Allostery; Covalent modification; Monomeric globin; Cytoglobin; Myoglobin; Neuroglobin
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 05 Jan 2015 11:36
Last Modified: 15 Jan 2022 00:34

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