Non-covalent and covalent modifications modulate the reactivity of monomeric mammalian globins.
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 cov...
Published in: | Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics |
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Online Access: | http://hdl.handle.net/11567/587554 https://doi.org/10.1016/j.bbapap.2013.02.012 |
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ftunivgenova:oai:iris.unige.it:11567/587554 2024-02-11T10:08:57+01:00 Non-covalent and covalent modifications modulate the reactivity of monomeric mammalian globins. Ascenzi P Marino M Polticelli F Coletta M Gioia M Marini S PESCE, ALESSANDRA Nardini M Bolognesi M Reeder BJ Wilson M.T. Ascenzi, P Marino, M Polticelli, F Coletta, M Gioia, M Marini, S Pesce, Alessandra Nardini, M Bolognesi, M Reeder, Bj Wilson, M. T. 2013 STAMPA http://hdl.handle.net/11567/587554 https://doi.org/10.1016/j.bbapap.2013.02.012 eng eng info:eu-repo/semantics/altIdentifier/pmid/23416443 info:eu-repo/semantics/altIdentifier/wos/WOS:000323191800009 volume:1834 firstpage:1750 lastpage:1756 numberofpages:7 journal:BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS http://hdl.handle.net/11567/587554 doi:10.1016/j.bbapap.2013.02.012 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84884636454 info:eu-repo/semantics/article 2013 ftunivgenova https://doi.org/10.1016/j.bbapap.2013.02.012 2024-01-17T17:43:52Z 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 O-2 and facilitates the O-2 flux within a myocyte, displays the allosteric modulation of the O-2 affinity on lactate, an obligatory product of glycolysis under anaerobic conditions, thus facilitating O-2 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, in turn, 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 to hypoxia. 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 on the lipid, such as oleate, binding which stabilizes the penta-coordination geometry of the heme-Fe atom. Lastly, the reactivity of NGB and CYGB is modulated 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 perspectives in cell survival and protection. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins. ... Article in Journal/Newspaper Sperm whale Università degli Studi di Genova: CINECA IRIS Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 1834 9 1750 1756 |
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Open Polar |
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Università degli Studi di Genova: CINECA IRIS |
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ftunivgenova |
language |
English |
description |
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 O-2 and facilitates the O-2 flux within a myocyte, displays the allosteric modulation of the O-2 affinity on lactate, an obligatory product of glycolysis under anaerobic conditions, thus facilitating O-2 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, in turn, 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 to hypoxia. 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 on the lipid, such as oleate, binding which stabilizes the penta-coordination geometry of the heme-Fe atom. Lastly, the reactivity of NGB and CYGB is modulated 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 perspectives in cell survival and protection. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins. ... |
author2 |
Ascenzi, P Marino, M Polticelli, F Coletta, M Gioia, M Marini, S Pesce, Alessandra Nardini, M Bolognesi, M Reeder, Bj Wilson, M. T. |
format |
Article in Journal/Newspaper |
author |
Ascenzi P Marino M Polticelli F Coletta M Gioia M Marini S PESCE, ALESSANDRA Nardini M Bolognesi M Reeder BJ Wilson M.T. |
spellingShingle |
Ascenzi P Marino M Polticelli F Coletta M Gioia M Marini S PESCE, ALESSANDRA Nardini M Bolognesi M Reeder BJ Wilson M.T. Non-covalent and covalent modifications modulate the reactivity of monomeric mammalian globins. |
author_facet |
Ascenzi P Marino M Polticelli F Coletta M Gioia M Marini S PESCE, ALESSANDRA Nardini M Bolognesi M Reeder BJ Wilson M.T. |
author_sort |
Ascenzi P |
title |
Non-covalent and covalent modifications modulate the reactivity of monomeric mammalian globins. |
title_short |
Non-covalent and covalent modifications modulate the reactivity of monomeric mammalian globins. |
title_full |
Non-covalent and covalent modifications modulate the reactivity of monomeric mammalian globins. |
title_fullStr |
Non-covalent and covalent modifications modulate the reactivity of monomeric mammalian globins. |
title_full_unstemmed |
Non-covalent and covalent modifications modulate the reactivity of monomeric mammalian globins. |
title_sort |
non-covalent and covalent modifications modulate the reactivity of monomeric mammalian globins. |
publishDate |
2013 |
url |
http://hdl.handle.net/11567/587554 https://doi.org/10.1016/j.bbapap.2013.02.012 |
genre |
Sperm whale |
genre_facet |
Sperm whale |
op_relation |
info:eu-repo/semantics/altIdentifier/pmid/23416443 info:eu-repo/semantics/altIdentifier/wos/WOS:000323191800009 volume:1834 firstpage:1750 lastpage:1756 numberofpages:7 journal:BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS http://hdl.handle.net/11567/587554 doi:10.1016/j.bbapap.2013.02.012 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84884636454 |
op_doi |
https://doi.org/10.1016/j.bbapap.2013.02.012 |
container_title |
Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics |
container_volume |
1834 |
container_issue |
9 |
container_start_page |
1750 |
op_container_end_page |
1756 |
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