Pilot--Toxicity of Lead at the Molecular Level

Brooklyn College, New York NY

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Abstract

Despite the fact that lead poisoning is a significant human health problem affecting almost one in twenty[unreadable] young children in the US, the mechanism of lead poisoning is not understood at the molecular level. Recent[unreadable] advances in neurobiology and human genetics have pinpointed two metalloproteins that are likely targets for[unreadable] lead in vivo: synaptotagmin (Syt), a calcium metalloprotein, and delta-aminolevulinic acid dehydratase[unreadable] (ALAD), a zinc metalloprotein. The goal of the proposed research is to advance out molecular understanding[unreadable] of lead toxicity and support active field of structural and spectroscopic investigations via a computational[unreadable] modeling of structural effects caused by lead substitution in zinc metalloproteins. Specifically, the aims of this[unreadable] study are (1) to determine and provide a molecular understanding of structural and spectral effects of lead's[unreadable] distinct preferences for highly asymmetrical tetra-coordinated structures, believed to be caused by a stable,[unreadable] inert outer lone pair of electrons, when it binds to typical structural zinc sites of metalloproteins, (2) to provide[unreadable] a molecular interpretation of Pb-cysteine charge-transfer bands and pinpoint its significance to reveal[unreadable] mechanisms of lead toxicity via resonance Raman spectroscopy when intertwined with theoretical[unreadable] predictions. By investigating lead's interactions and effects on typical structural zinc sites of metalloproteins[unreadable] and numerous model compounds we seek to gain a broad understanding of the mechanisms of lead toxicity.[unreadable] Furthermore, the studies proposed herein will provide the foundation for future studies by providing accurate[unreadable] and reliable methodologies for computational investigations of other heavy metal poisoning by such[unreadable] elements as mercury, cadmium and arsenic.