Protein Structure and Spectral Analysis
Lawrence J. Berliner, Professor
We use unpaired electrons to probe dynamics and distances between selected sites on a protein that are sensitive to it's unique structure and function. This may be substituting a paramagnetic lanthanide for a calcium ion or by covalently adding novel aminoxyl radical probes called spin labels. The spectral analyses, including distance measurements between probes, provides insight on how a protein folds and important conformational changes associated with function.
Additionally we use molecules called spin traps to characterize free radicals in vivo. Some studies are important to health problems ranging from ischemia/heart disease to infection shock. We pioneered development of techniques and instrumentation for live animal applications which are now routine in unique laboratories around the world. We also utilize MRI in these in vivo applications. Current research involves a homologous family of calcium binding proteins that have tumor killing properties in molten globule form. These also form amyloid aggregates and fibrils, which may be excellent models for neurodegenerative disease proteins.
The free radical project involves intermediates of a common blood pressure lowering drug that may lead to heart disease. The work includes protein expression and labeling, spectroscopic measurements by magnetic resonance, fluorescence, CD and subsequent data analysis.