The investigators will develop the first instrument to detect Zinc spectroscopically in biophysical samples. Zinc (Zn) is one of the most important transition metal ions in biology and one of the most difficult one to detect. It is the second most prevalent transition metal ion in biology after iron. In addition to Zn's role at the active site of a variety of enzymes and as a structural element in others, Zn plays a dominant role in proteins (so-called 'Zn fingers') which control the flow of genetic information through direct interactions with the nucleic acids (DNA and RNA). The investigator proposes studying Zn spectroscopically using SQUID-detected nuclear quadruple double resonance. Zinc is spectroscopically silent. It is found in only one oxidation state in biology - namely the Zn(II) state which has a d(10) filled shell configuration. Thus, it is optically silent and diamagnetic, and therefore undetectable by either electron paramagnetic resonance (EPR), variable field magnetic circular dichroism (CD), or magnetic susceptibility. Nuclear magnetic resonance (NMR) detection of Zn is difficult because its two most prevalent isotopes have zero nuclear spin while the third (67)Zn has nuclear spin 5/2 with an abundance of 4%. Quadruple nuclei of this low abundance require specialized NMR techniques which are not yet routinely available within the biochemical or biophysical research communities. The investigator will apply these specialized techniques to build a new spectrometer capable of detecting Zn spectroscopically for the first time in biophysical samples. Other biologically important nuclei which could be studied using the same instrument include: (2)H, (14)N, (23)Na, (17)O, (25)Mg, (33)S, (35)C1, (37)C1, (39)K, (43)Ca, (51)V, (59)Co, (63)Cu, (65)Cu, (55)Mn, (95)Mo, (97)Mo, and (127)I. The proposed instrument therefore has the potential for use in a broad range of structural studies of biological molecules.
