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

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. Graphical abstract .

SUBMITTER: Villasenor-Granados T

PROVIDER: S-EPMC6592991 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Determination of Pb-210 (210Pb) in aqueous solution is a common radioanalytical challenge in environmental science. Widely used methods for undertaking these analyses (e.g., ASTM D7535) rely on the use of stable lead (Pb) as a yield tracer that takes into account losses of 210Pb that inevitably occur during elemental/radiochemical separations of the procedures. Although effective, these methods introduce technical challenges that can be difficult to track and potentially introduce uncertainty that can be difficult to quantify. Examples of these challenges include interference from endogenous stable Pb in complex sample matrices; contamination of stable Pb carrier with 210Pb; and high detection limits due to counting efficiency limitations. We hypothesized that many of these challenges could be avoided by the use of the electron-capture, gamma-emitting isotope, 203Pb as a chemical yield tracer in the analysis of 210Pb. A series of experiments were performed to evaluate the efficacy of 203Pb as a tracer. Four different matrices were analyzed, including a complex matrix (hydraulic-fracturing produced fluids); and samples comprising less complicated matrices (i.e., river water, deionized water, and tap water). Separation techniques and counting methodologies were also compared and optimized. Due to a relatively short-half life (52 h), 203Pb tracer is effectively massless for the purposes of chemical separations, allowing for reduced chromatography column resin bed volumes. Because 203Pb is a gamma emitter (279 keV; 81% intensity), recovery can be determined non-destructively in a variety of matrices, including liquid scintillation cocktail. The use of liquid scintillation as a counting methodology allowed for determination of 210Pb activities via 210Pb or 210Po; and recoveries of greater than 90% are routinely achievable using this approach. The improved method for the analysis of 210Pb in aqueous matrices allows for the analysis of complex matrices, at reduced cost, while providing greater counting flexibility in achieving acceptable detections limits.

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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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