Biophysical chemistry is an emerging area of science that utilizes physical chemistry techniques such as fluorescence spectroscopy, X-ray crystallography, small angle scattering and microscopy to study biological systems. These techniques provide avenues for not only analyzing biochemical events relevant to specific disease states, but also provide insight for mechanisms to modulate crucial protein activity. The work presented will focus on using these techniques to study two different protein families shown to be important in tumorgenesis and cancer progression: aldehyde dehydrogenases (ALDHs) and angiomotin (Amot).<br/><br/>Human ALDHs comprise a family of 17 homologous enzymes that metabolize different biogenic and exogenic aldehydes. ALDH1A1 overexpression has been used as a biomarker for a variety of cancers, including high grade ductal carcinoma, multiple myeloma and acute myeloid leukemia; while ALDH3A1 overexpression confers resistance to cyclophosphamide treatment of cancer cells. This work will present a summary of the discovery of enzyme specific classes of inhibitors based on data from kinetic studies and crystallographic analyses, which demonstrates the mechanism of inhibition rationale for enzyme specificity.<br/><br/>Amots are membrane associated and directly integrate the signaling that controls cellular differentiation and cell growth. These proteins all have an essential lipid binding domain with the ability to highly discriminate for membranes enriched in monophosphorylated phosphatidylinositols, followed by membrane deformation. This work will show how analytical sedimentation, small angle scattering, fluorescence spectroscopy and cell based microscopy assays are being employed to determine the mechanisms by which membrane proteins are targeted to these specific lipid mixtures.

Using biophysical chemistry to modulate the activity of aldehyde dehydrogenases and Amot family proteins

250th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.