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Abstract:

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.

Registro:

Documento: Artículo
Título:NMR and molecular dynamics studies of the interaction of melatonin with calmodulin
Autor:Turjanski, A.G.; Estrin, D.A.; Rosenstein, R.E.; Mccormick, J.E.; Martin, S.R.; Pastore, A.; Biekofsky, R.R.; Martorana, V.
Filiación:Depto. Quim. Inorg., Analitica Y Q., Inst. Quim. Fis. Mat., Medio A., Fac. de Ciencias Exactas Y Naturales, Buenos Aires, Argentina
Lab. Neuroquimica Retiniana Y O., Depto. de Bioquímica Humana, Universidad de Buenos Aires, Buenos Aires, Argentina
Molecular Structure Division, Natl. Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom
Consiglio Nazionale Delle Ricerche, Istituto di Biofisica (Palermo), I-90147, Palermo, Italy
CNR-IBF, Istituto di Biofisica (Palermo), via U. La Malfa 153, I-90147, Palermo, Italy
Palabras clave: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
Año:2004
Volumen:13
Número:11
Página de inicio:2925
Página de fin:2938
DOI: http://dx.doi.org/10.1110/ps.04611404
Título revista:Protein Science
Título revista abreviado:Protein Sci.
ISSN:09618368
CODEN:PRCIE
CAS:calcium, 7440-70-2; melatonin, 73-31-4; Calcium, 7440-70-2; Calmodulin; Drosophila Proteins; Melatonin, 73-31-4
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_09618368_v13_n11_p2925_Turjanski.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09618368_v13_n11_p2925_Turjanski

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Citas:

---------- APA ----------
Turjanski, A.G., Estrin, D.A., Rosenstein, R.E., Mccormick, J.E., Martin, S.R., Pastore, A., Biekofsky, R.R.,..., Martorana, V. (2004) . NMR and molecular dynamics studies of the interaction of melatonin with calmodulin. Protein Science, 13(11), 2925-2938.
http://dx.doi.org/10.1110/ps.04611404
---------- CHICAGO ----------
Turjanski, A.G., Estrin, D.A., Rosenstein, R.E., Mccormick, J.E., Martin, S.R., Pastore, A., et al. "NMR and molecular dynamics studies of the interaction of melatonin with calmodulin" . Protein Science 13, no. 11 (2004) : 2925-2938.
http://dx.doi.org/10.1110/ps.04611404
---------- MLA ----------
Turjanski, A.G., Estrin, D.A., Rosenstein, R.E., Mccormick, J.E., Martin, S.R., Pastore, A., et al. "NMR and molecular dynamics studies of the interaction of melatonin with calmodulin" . Protein Science, vol. 13, no. 11, 2004, pp. 2925-2938.
http://dx.doi.org/10.1110/ps.04611404
---------- VANCOUVER ----------
Turjanski, A.G., Estrin, D.A., Rosenstein, R.E., Mccormick, J.E., Martin, S.R., Pastore, A., et al. NMR and molecular dynamics studies of the interaction of melatonin with calmodulin. Protein Sci. 2004;13(11):2925-2938.
http://dx.doi.org/10.1110/ps.04611404