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

Autores
Turjanski, A.G.; Estrin, D.A.; Rosenstein, R.E.; Mccormick, J.E.; Martin, S.R.; Pastore, A.; Biekofsky, R.R.; Martorana, V.
Año de publicación
2004
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fuente
Protein Sci. 2004;13(11):2925-2938
Materia
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
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/2.5/ar
Repositorio
Biblioteca Digital (UBA-FCEN)
Institución
Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
OAI Identificador
paperaa:paper_09618368_v13_n11_p2925_Turjanski
Acceder
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oai_identifier_str paperaa:paper_09618368_v13_n11_p2925_Turjanski
network_acronym_str BDUBAFCEN
repository_id_str 1896
network_name_str Biblioteca Digital (UBA-FCEN)
spelling NMR and molecular dynamics studies of the interaction of melatonin with calmodulinTurjanski, A.G.Estrin, D.A.Rosenstein, R.E.Mccormick, J.E.Martin, S.R.Pastore, A.Biekofsky, R.R.Martorana, V.CalmodulinFluorescenceMelatoninMolecular dynamicsNMRWeak interactionscalciumcalmodulinmelatoninamino terminal sequencearticlebinding affinitycarboxy terminal sequencecorrelation analysisfluorescence spectroscopymolecular dynamicsmolecular interactionmonitoringnuclear magnetic resonance spectroscopypriority journalprotein domainprotein interactionsimulationtitrimetryBinding SitesCalciumCalmodulinComputer SimulationDrosophila ProteinsMelatoninModels, MolecularMotionNuclear Magnetic Resonance, BiomolecularProtein BindingPineal 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.2004info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://hdl.handle.net/20.500.12110/paper_09618368_v13_n11_p2925_TurjanskiProtein Sci. 2004;13(11):2925-2938reponame:Biblioteca Digital (UBA-FCEN)instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesinstacron:UBA-FCENenginfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/2.5/ar2025-10-23T11:18:28Zpaperaa:paper_09618368_v13_n11_p2925_TurjanskiInstitucionalhttps://digital.bl.fcen.uba.ar/Universidad públicaNo correspondehttps://digital.bl.fcen.uba.ar/cgi-bin/oaiserver.cgiana@bl.fcen.uba.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:18962025-10-23 11:18:29.379Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturalesfalse
dc.title.none.fl_str_mv NMR and molecular dynamics studies of the interaction of melatonin with calmodulin
title NMR and molecular dynamics studies of the interaction of melatonin with calmodulin
spellingShingle NMR and molecular dynamics studies of the interaction of melatonin with calmodulin
Turjanski, A.G.
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
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
dc.creator.none.fl_str_mv Turjanski, A.G.
Estrin, D.A.
Rosenstein, R.E.
Mccormick, J.E.
Martin, S.R.
Pastore, A.
Biekofsky, R.R.
Martorana, V.
author Turjanski, A.G.
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_role author
author2 Estrin, D.A.
Rosenstein, R.E.
Mccormick, J.E.
Martin, S.R.
Pastore, A.
Biekofsky, R.R.
Martorana, V.
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv 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
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
dc.description.none.fl_txt_mv 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.
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.
publishDate 2004
dc.date.none.fl_str_mv 2004
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12110/paper_09618368_v13_n11_p2925_Turjanski
url http://hdl.handle.net/20.500.12110/paper_09618368_v13_n11_p2925_Turjanski
dc.language.none.fl_str_mv eng
language eng
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/2.5/ar
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/2.5/ar
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Protein Sci. 2004;13(11):2925-2938
reponame:Biblioteca Digital (UBA-FCEN)
instname:Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
instacron:UBA-FCEN
reponame_str Biblioteca Digital (UBA-FCEN)
collection Biblioteca Digital (UBA-FCEN)
instname_str Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
instacron_str UBA-FCEN
institution UBA-FCEN
repository.name.fl_str_mv Biblioteca Digital (UBA-FCEN) - Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales
repository.mail.fl_str_mv ana@bl.fcen.uba.ar
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score 12.982451

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