NMR and molecular dynamics studies of the interaction of melatonin with calmodulin
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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2004
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09618368_v13_n11_p2925_Turjanski http://hdl.handle.net/20.500.12110/paper_09618368_v13_n11_p2925_Turjanski |
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paper:paper_09618368_v13_n11_p2925_Turjanski2023-06-08T15:57:58Z NMR and molecular dynamics studies of the interaction of melatonin with calmodulin Turjanski, Adrián Gustavo Estrin, Dario Ariel Rosenstein, Ruth Estela Biekofsky, Rodolfo Roberto 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 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. 2004 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09618368_v13_n11_p2925_Turjanski http://hdl.handle.net/20.500.12110/paper_09618368_v13_n11_p2925_Turjanski |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (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, Adrián Gustavo Estrin, Dario Ariel Rosenstein, Ruth Estela Biekofsky, Rodolfo Roberto 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. |
| author |
Turjanski, Adrián Gustavo Estrin, Dario Ariel Rosenstein, Ruth Estela Biekofsky, Rodolfo Roberto |
| author_facet |
Turjanski, Adrián Gustavo Estrin, Dario Ariel Rosenstein, Ruth Estela Biekofsky, Rodolfo Roberto |
| author_sort |
Turjanski, Adrián Gustavo |
| 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 |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09618368_v13_n11_p2925_Turjanski http://hdl.handle.net/20.500.12110/paper_09618368_v13_n11_p2925_Turjanski |
| work_keys_str_mv |
AT turjanskiadriangustavo nmrandmoleculardynamicsstudiesoftheinteractionofmelatoninwithcalmodulin AT estrindarioariel nmrandmoleculardynamicsstudiesoftheinteractionofmelatoninwithcalmodulin AT rosensteinruthestela nmrandmoleculardynamicsstudiesoftheinteractionofmelatoninwithcalmodulin AT biekofskyrodolforoberto nmrandmoleculardynamicsstudiesoftheinteractionofmelatoninwithcalmodulin |
| _version_ |
1768544189780328448 |