NMR and molecular dynamics studies of the interaction of melatonin with calmodulin

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Pineal hormone melatonin (N-acetyl-5-methoxytryptamine) is thought to modulate the calcium/calmodulin signaling pathway either by changing intracellular Ca2+ concentration via activation of its G-protein-coupled membrane receptors, or through a direct interaction with calmodulin (CaM). The present w...

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Autores principales:	Turjanski, A.G., Estrin, D.A., Rosenstein, R.E., Mccormick, J.E., Martin, S.R., Pastore, A., Biekofsky, R.R., Martorana, V.
Formato:	Artículo publishedVersion
Publicado:	2004
Materias:	Calmodulin Fluorescence Melatonin Molecular dynamics NMR Weak interactions calcium calmodulin melatonin amino terminal sequence article binding affinity carboxy terminal sequence correlation analysis fluorescence spectroscopy molecular dynamics molecular interaction monitoring nuclear magnetic resonance spectroscopy priority journal protein domain protein interaction simulation titrimetry Binding Sites Calcium Computer Simulation Drosophila Proteins Models, Molecular Motion Nuclear Magnetic Resonance, Biomolecular Protein Binding
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_09618368_v13_n11_p2925_Turjanski https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_09618368_v13_n11_p2925_Turjanski_oai
Aporte de:	Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires

id	I28-R145-paper_09618368_v13_n11_p2925_Turjanski_oai
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spelling	I28-R145-paper_09618368_v13_n11_p2925_Turjanski_oai2024-08-16 Turjanski, A.G. Estrin, D.A. Rosenstein, R.E. Mccormick, J.E. Martin, S.R. Pastore, A. Biekofsky, R.R. Martorana, V. 2004 Pineal hormone melatonin (N-acetyl-5-methoxytryptamine) is thought to modulate the calcium/calmodulin signaling pathway either by changing intracellular Ca2+ concentration via activation of its G-protein-coupled membrane receptors, or through a direct interaction with calmodulin (CaM). The present work studies the direct interaction of melatonin with intact calcium-saturated CaM both experimentally, by fluorescence and nuclear magnetic resonance spectroscopies, and theoretically, by molecular dynamics simulations. The analysis of the experimental data shows that the interaction is calcium-dependent. The affinity, as obtained from monitoring 15N and 1H chemical shift changes for a melatonin titration, is weak (in the millimolar range) and comparable for the N- and C-terminal domains. Partial replacement of diamagnetic Ca2+ by paramagnetic Tb3+ allowed the measurement of interdomain NMR pseudocontact shifts and residual dipolar couplings, indicating that each domain movement in the complex is not correlated with the other one. Molecular dynamics simulations allow us to follow the dynamics of melatonin in the binding pocket of CaM. Overall, this study provides an example of how a combination of experimental and theoretical approaches can shed light on a weakly interacting system of biological and pharmacological significance. Fil:Turjanski, A.G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Rosenstein, R.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Biekofsky, R.R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. application/pdf http://hdl.handle.net/20.500.12110/paper_09618368_v13_n11_p2925_Turjanski info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar Protein Sci. 2004;13(11):2925-2938 Calmodulin Fluorescence Melatonin Molecular dynamics NMR Weak interactions calcium calmodulin melatonin amino terminal sequence article binding affinity carboxy terminal sequence correlation analysis fluorescence spectroscopy molecular dynamics molecular interaction monitoring nuclear magnetic resonance spectroscopy priority journal protein domain protein interaction simulation titrimetry Binding Sites Calcium Calmodulin Computer Simulation Drosophila Proteins Melatonin Models, Molecular Motion Nuclear Magnetic Resonance, Biomolecular Protein Binding NMR and molecular dynamics studies of the interaction of melatonin with calmodulin info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_09618368_v13_n11_p2925_Turjanski_oai
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-145
collection	Repositorio Digital de la Universidad de Buenos Aires (UBA)
topic	Calmodulin Fluorescence Melatonin Molecular dynamics NMR Weak interactions calcium calmodulin melatonin amino terminal sequence article binding affinity carboxy terminal sequence correlation analysis fluorescence spectroscopy molecular dynamics molecular interaction monitoring nuclear magnetic resonance spectroscopy priority journal protein domain protein interaction simulation titrimetry Binding Sites Calcium Calmodulin Computer Simulation Drosophila Proteins Melatonin Models, Molecular Motion Nuclear Magnetic Resonance, Biomolecular Protein Binding
spellingShingle	Calmodulin Fluorescence Melatonin Molecular dynamics NMR Weak interactions calcium calmodulin melatonin amino terminal sequence article binding affinity carboxy terminal sequence correlation analysis fluorescence spectroscopy molecular dynamics molecular interaction monitoring nuclear magnetic resonance spectroscopy priority journal protein domain protein interaction simulation titrimetry Binding Sites Calcium Calmodulin Computer Simulation Drosophila Proteins Melatonin Models, Molecular Motion Nuclear Magnetic Resonance, Biomolecular Protein Binding Turjanski, A.G. Estrin, D.A. Rosenstein, R.E. Mccormick, J.E. Martin, S.R. Pastore, A. Biekofsky, R.R. Martorana, V. NMR and molecular dynamics studies of the interaction of melatonin with calmodulin
topic_facet	Calmodulin Fluorescence Melatonin Molecular dynamics NMR Weak interactions calcium calmodulin melatonin amino terminal sequence article binding affinity carboxy terminal sequence correlation analysis fluorescence spectroscopy molecular dynamics molecular interaction monitoring nuclear magnetic resonance spectroscopy priority journal protein domain protein interaction simulation titrimetry Binding Sites Calcium Calmodulin Computer Simulation Drosophila Proteins Melatonin Models, Molecular Motion Nuclear Magnetic Resonance, Biomolecular Protein Binding
description	Pineal hormone melatonin (N-acetyl-5-methoxytryptamine) is thought to modulate the calcium/calmodulin signaling pathway either by changing intracellular Ca2+ concentration via activation of its G-protein-coupled membrane receptors, or through a direct interaction with calmodulin (CaM). The present work studies the direct interaction of melatonin with intact calcium-saturated CaM both experimentally, by fluorescence and nuclear magnetic resonance spectroscopies, and theoretically, by molecular dynamics simulations. The analysis of the experimental data shows that the interaction is calcium-dependent. The affinity, as obtained from monitoring 15N and 1H chemical shift changes for a melatonin titration, is weak (in the millimolar range) and comparable for the N- and C-terminal domains. Partial replacement of diamagnetic Ca2+ by paramagnetic Tb3+ allowed the measurement of interdomain NMR pseudocontact shifts and residual dipolar couplings, indicating that each domain movement in the complex is not correlated with the other one. Molecular dynamics simulations allow us to follow the dynamics of melatonin in the binding pocket of CaM. Overall, this study provides an example of how a combination of experimental and theoretical approaches can shed light on a weakly interacting system of biological and pharmacological significance.
format	Artículo Artículo publishedVersion
author	Turjanski, A.G. Estrin, D.A. Rosenstein, R.E. Mccormick, J.E. Martin, S.R. Pastore, A. Biekofsky, R.R. Martorana, V.
author_facet	Turjanski, A.G. Estrin, D.A. Rosenstein, R.E. Mccormick, J.E. Martin, S.R. Pastore, A. Biekofsky, R.R. Martorana, V.
author_sort	Turjanski, A.G.
title	NMR and molecular dynamics studies of the interaction of melatonin with calmodulin
title_short	NMR and molecular dynamics studies of the interaction of melatonin with calmodulin
title_full	NMR and molecular dynamics studies of the interaction of melatonin with calmodulin
title_fullStr	NMR and molecular dynamics studies of the interaction of melatonin with calmodulin
title_full_unstemmed	NMR and molecular dynamics studies of the interaction of melatonin with calmodulin
title_sort	nmr and molecular dynamics studies of the interaction of melatonin with calmodulin
publishDate	2004
url	http://hdl.handle.net/20.500.12110/paper_09618368_v13_n11_p2925_Turjanski https://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=artiaex&d=paper_09618368_v13_n11_p2925_Turjanski_oai
work_keys_str_mv	AT turjanskiag nmrandmoleculardynamicsstudiesoftheinteractionofmelatoninwithcalmodulin AT estrinda nmrandmoleculardynamicsstudiesoftheinteractionofmelatoninwithcalmodulin AT rosensteinre nmrandmoleculardynamicsstudiesoftheinteractionofmelatoninwithcalmodulin AT mccormickje nmrandmoleculardynamicsstudiesoftheinteractionofmelatoninwithcalmodulin AT martinsr nmrandmoleculardynamicsstudiesoftheinteractionofmelatoninwithcalmodulin AT pastorea nmrandmoleculardynamicsstudiesoftheinteractionofmelatoninwithcalmodulin AT biekofskyrr nmrandmoleculardynamicsstudiesoftheinteractionofmelatoninwithcalmodulin AT martoranav nmrandmoleculardynamicsstudiesoftheinteractionofmelatoninwithcalmodulin
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NMR and molecular dynamics studies of the interaction of melatonin with calmodulin

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