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

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Minority Biomedical Research Support - MBRS (S06)
Project #
5S06GM076168-02
Application #
7558775
Study Section
Minority Programs Review Committee (MPRC)
Project Start
Project End
Budget Start
2007-03-01
Budget End
2008-02-29
Support Year
2
Fiscal Year
2007
Total Cost
$73,893
Indirect Cost
Name
Brooklyn College
Department
Type
DUNS #
620127691
City
New York
State
NY
Country
United States
Zip Code
11210
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