Plications of extended ultra-violet circular dichroism spectroscopy in biology and medicine.
Deep ultra-violet circular dichroism is fast becoming an important technique in structural biology. The exponential increase in the number of protein structures deposited in the Protein Data Bank together with programs that extract protein secondary structure from atomic coordinates and the advancement of the software to analyse circular dichroic spectra, have revolutionised the technique. In addition, the extended short wavelength data afforded by synchrotron radiation is set to have a major impact on the development of the area. We have selected three diverse areas of research and development in the biomedical sciences to illustrate the ubiquity of the technique for future applications in the area of biomedical research. For example, the high flux of synchrotron radiation has provided a gold standard for the assay of the lipoprotein HDL in serum which has been proven to reverse the effects of coronary heart disease. In a second example, the high flux of synchrotron radiation enables the recording of millisecond data during the conformational changes in proteins over their spectrum, mapping out changes to protein secondary structure and thus providing absolute structural measurements in the millisecond time regime. In the third example, subtle conformational changes are interpreted from the extended CD spectra on protein drug binding, distinguishing between induced binding effects and the conformational changes in the target protein. The strengths and weaknesses of extended ultra-violet circular dichroism using synchrotron radiation are discussed using these examples as a template.
Jones
Gareth R
GR
CCLRC Daresbury Laboratory, Warrington, UK.
Clarke
David T
DT
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D002942:Circular Dichroism / Q000379:methods*; D006801:Humans; D011485:Protein Binding; D011487:Protein Conformation; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D017356:Synchrotrons
D000806:Angiotensin-Converting Enzyme Inhibitors; D008076:Cholesterol, HDL