Cargando…

Reciprocal Allosteric Modulation of Carbon Monoxide and Warfarin Binding to Ferrous Human Serum Heme-Albumin

Human serum albumin (HSA), the most abundant protein in human plasma, could be considered as a prototypic monomeric allosteric protein, since the ligand-dependent conformational adaptability of HSA spreads beyond the immediate proximity of the binding site(s). As a matter of fact, HSA is a major tra...

Descripción completa

Detalles Bibliográficos
Autores principales: Bocedi, Alessio, De Sanctis, Giampiero, Ciaccio, Chiara, Tundo, Grazia R., Di Masi, Alessandra, Fanali, Gabriella, Nicoletti, Francesco P., Fasano, Mauro, Smulevich, Giulietta, Ascenzi, Paolo, Coletta, Massimo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605432/
https://www.ncbi.nlm.nih.gov/pubmed/23555601
http://dx.doi.org/10.1371/journal.pone.0058842
_version_ 1782263890273370112
author Bocedi, Alessio
De Sanctis, Giampiero
Ciaccio, Chiara
Tundo, Grazia R.
Di Masi, Alessandra
Fanali, Gabriella
Nicoletti, Francesco P.
Fasano, Mauro
Smulevich, Giulietta
Ascenzi, Paolo
Coletta, Massimo
author_facet Bocedi, Alessio
De Sanctis, Giampiero
Ciaccio, Chiara
Tundo, Grazia R.
Di Masi, Alessandra
Fanali, Gabriella
Nicoletti, Francesco P.
Fasano, Mauro
Smulevich, Giulietta
Ascenzi, Paolo
Coletta, Massimo
author_sort Bocedi, Alessio
collection PubMed
description Human serum albumin (HSA), the most abundant protein in human plasma, could be considered as a prototypic monomeric allosteric protein, since the ligand-dependent conformational adaptability of HSA spreads beyond the immediate proximity of the binding site(s). As a matter of fact, HSA is a major transport protein in the bloodstream and the regulation of the functional allosteric interrelationships between the different binding sites represents a fundamental information for the knowledge of its transport function. Here, kinetics and thermodynamics of the allosteric modulation: (i) of carbon monoxide (CO) binding to ferrous human serum heme-albumin (HSA-heme-Fe(II)) by warfarin (WF), and (ii) of WF binding to HSA-heme-Fe(II) by CO are reported. All data were obtained at pH 7.0 and 25°C. Kinetics of CO and WF binding to the FA1 and FA7 sites of HSA-heme-Fe(II), respectively, follows a multi-exponential behavior (with the same relative percentage for the two ligands). This can be accounted for by the existence of multiple conformations and/or heme-protein axial coordination forms of HSA-heme-Fe(II). The HSA-heme-Fe(II) populations have been characterized by resonance Raman spectroscopy, indicating the coexistence of different species characterized by four-, five- and six-coordination of the heme-Fe atom. As a whole, these results suggest that: (i) upon CO binding a conformational change of HSA-heme-Fe(II) takes place (likely reflecting the displacement of an endogenous ligand by CO), and (ii) CO and/or WF binding brings about a ligand-dependent variation of the HSA-heme-Fe(II) population distribution of the various coordinating species. The detailed thermodynamic and kinetic analysis here reported allows a quantitative description of the mutual allosteric effect of CO and WF binding to HSA-heme-Fe(II).
format Online
Article
Text
id pubmed-3605432
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-36054322013-04-03 Reciprocal Allosteric Modulation of Carbon Monoxide and Warfarin Binding to Ferrous Human Serum Heme-Albumin Bocedi, Alessio De Sanctis, Giampiero Ciaccio, Chiara Tundo, Grazia R. Di Masi, Alessandra Fanali, Gabriella Nicoletti, Francesco P. Fasano, Mauro Smulevich, Giulietta Ascenzi, Paolo Coletta, Massimo PLoS One Research Article Human serum albumin (HSA), the most abundant protein in human plasma, could be considered as a prototypic monomeric allosteric protein, since the ligand-dependent conformational adaptability of HSA spreads beyond the immediate proximity of the binding site(s). As a matter of fact, HSA is a major transport protein in the bloodstream and the regulation of the functional allosteric interrelationships between the different binding sites represents a fundamental information for the knowledge of its transport function. Here, kinetics and thermodynamics of the allosteric modulation: (i) of carbon monoxide (CO) binding to ferrous human serum heme-albumin (HSA-heme-Fe(II)) by warfarin (WF), and (ii) of WF binding to HSA-heme-Fe(II) by CO are reported. All data were obtained at pH 7.0 and 25°C. Kinetics of CO and WF binding to the FA1 and FA7 sites of HSA-heme-Fe(II), respectively, follows a multi-exponential behavior (with the same relative percentage for the two ligands). This can be accounted for by the existence of multiple conformations and/or heme-protein axial coordination forms of HSA-heme-Fe(II). The HSA-heme-Fe(II) populations have been characterized by resonance Raman spectroscopy, indicating the coexistence of different species characterized by four-, five- and six-coordination of the heme-Fe atom. As a whole, these results suggest that: (i) upon CO binding a conformational change of HSA-heme-Fe(II) takes place (likely reflecting the displacement of an endogenous ligand by CO), and (ii) CO and/or WF binding brings about a ligand-dependent variation of the HSA-heme-Fe(II) population distribution of the various coordinating species. The detailed thermodynamic and kinetic analysis here reported allows a quantitative description of the mutual allosteric effect of CO and WF binding to HSA-heme-Fe(II). Public Library of Science 2013-03-21 /pmc/articles/PMC3605432/ /pubmed/23555601 http://dx.doi.org/10.1371/journal.pone.0058842 Text en © 2013 Bocedi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bocedi, Alessio
De Sanctis, Giampiero
Ciaccio, Chiara
Tundo, Grazia R.
Di Masi, Alessandra
Fanali, Gabriella
Nicoletti, Francesco P.
Fasano, Mauro
Smulevich, Giulietta
Ascenzi, Paolo
Coletta, Massimo
Reciprocal Allosteric Modulation of Carbon Monoxide and Warfarin Binding to Ferrous Human Serum Heme-Albumin
title Reciprocal Allosteric Modulation of Carbon Monoxide and Warfarin Binding to Ferrous Human Serum Heme-Albumin
title_full Reciprocal Allosteric Modulation of Carbon Monoxide and Warfarin Binding to Ferrous Human Serum Heme-Albumin
title_fullStr Reciprocal Allosteric Modulation of Carbon Monoxide and Warfarin Binding to Ferrous Human Serum Heme-Albumin
title_full_unstemmed Reciprocal Allosteric Modulation of Carbon Monoxide and Warfarin Binding to Ferrous Human Serum Heme-Albumin
title_short Reciprocal Allosteric Modulation of Carbon Monoxide and Warfarin Binding to Ferrous Human Serum Heme-Albumin
title_sort reciprocal allosteric modulation of carbon monoxide and warfarin binding to ferrous human serum heme-albumin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3605432/
https://www.ncbi.nlm.nih.gov/pubmed/23555601
http://dx.doi.org/10.1371/journal.pone.0058842
work_keys_str_mv AT bocedialessio reciprocalallostericmodulationofcarbonmonoxideandwarfarinbindingtoferroushumanserumhemealbumin
AT desanctisgiampiero reciprocalallostericmodulationofcarbonmonoxideandwarfarinbindingtoferroushumanserumhemealbumin
AT ciacciochiara reciprocalallostericmodulationofcarbonmonoxideandwarfarinbindingtoferroushumanserumhemealbumin
AT tundograziar reciprocalallostericmodulationofcarbonmonoxideandwarfarinbindingtoferroushumanserumhemealbumin
AT dimasialessandra reciprocalallostericmodulationofcarbonmonoxideandwarfarinbindingtoferroushumanserumhemealbumin
AT fanaligabriella reciprocalallostericmodulationofcarbonmonoxideandwarfarinbindingtoferroushumanserumhemealbumin
AT nicolettifrancescop reciprocalallostericmodulationofcarbonmonoxideandwarfarinbindingtoferroushumanserumhemealbumin
AT fasanomauro reciprocalallostericmodulationofcarbonmonoxideandwarfarinbindingtoferroushumanserumhemealbumin
AT smulevichgiulietta reciprocalallostericmodulationofcarbonmonoxideandwarfarinbindingtoferroushumanserumhemealbumin
AT ascenzipaolo reciprocalallostericmodulationofcarbonmonoxideandwarfarinbindingtoferroushumanserumhemealbumin
AT colettamassimo reciprocalallostericmodulationofcarbonmonoxideandwarfarinbindingtoferroushumanserumhemealbumin