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Binding of Pb-Melatonin and Pb-(Melatonin-metabolites) complexes with DMT1 and ZIP8: implications for lead detoxification

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Abstract

We have applied the docking methodology to characterize the binding modes of the divalent metal transporter 1 (DMT1) and the zinc transporter 8 (ZIP8) protein channels with: melatonin, some melatonin metabolites, and a few lead complexes of melatonin and its metabolites, in three different coordination modes (mono-coordinated, bi-coordinated and tri-coordinated). Our results show that bi-coordinated and tri-coordinated lead complexes prefer to bind inside the central region of ZIP8. Moreover, the interaction strength is larger compared with that of the free melatonin and melatonin metabolites. On the other hand, the binding modes with DMT1 of such complexes display lower binding energies, compared with the free melatonin and melatonin metabolites. Our results suggest that ZIP8 plays a major role in the translocation of Pb, bi or tri coordinated, when melatonin metabolites are present. Finally, we have characterized the binding modes responsible for the ZIP8 large affinities, found in bi-coordinated and tri-coordinated lead complexes. Our results show that such interactions are greater, because of an increase of the number of hydrogen bonds, the number and intensity of electrostatic interactions, and the interaction overlay degree in each binding mode. Our results give insight into the importance of the ZIP8 channel on lead transport and a possible elimination mechanism in lead detoxification processes.

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Acknowledgments

National Laboratory UG-UAA-CONACyT (123732) is acknowledged for computing resources. Authors are thankful to DAIP-Universidad de Guanajuato (“Convocatoria Institucional de Apoyo a la Investigación Científica 2016-2017”, for funding through project No. 736/2016) and PRODEP (SEP-México) for financial support.

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Authors and Affiliations

  1. Departamento de Química, Centro de Investigaciones y de Estudios Avanzados del Instituto Politécnico Nacional, Zacatenco, Ciudad de México, Mexico

    Tayde Villaseñor-Granados

  2. Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N, C. P. 36050, Guanajuato, Gto., Mexico

    Tayde Villaseñor-Granados, Erik Díaz-Cervantes, Karla J. Soto-Arredondo, Minerva Martínez-Alfaro & Juvencio Robles

  3. Departamento de Alimentos, Centro Interdisciplinario del Noreste (CINUG), Universidad de Guanajuato, 37975 Tierra Blanca, Guanajuato, Mexico

    Erik Díaz-Cervantes

  4. Departamento de Química, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Noria Alta S/N, C. P. 36050, Guanajuato, Guanajuato, Gto., Mexico

    Marco A. García-Revilla

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Villaseñor-Granados, T., Díaz-Cervantes, E., Soto-Arredondo, K.J. et al. Binding of Pb-Melatonin and Pb-(Melatonin-metabolites) complexes with DMT1 and ZIP8: implications for lead detoxification. DARU J Pharm Sci 27, 137–148 (2019). https://doi.org/10.1007/s40199-019-00256-5

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