Enzymatic incorporation of selenium into RNA and DNA for structure study

CARB 72

Zhen Huang, Huang@gsu.edu, Gary E. Brandt, gbrandt1@student.gsu.edu, Nicolas Carrasco, and Julianne Caton-Williams, jcwill_tt@yahoo.com. Department of Chemistry, Georgia State University, 38 Peachtree Center Avenue, Atlanta, GA 30303-3083
X-ray crystallography is the most direct and powerful tool for 3-D structure determination of bio-macromolecules, such as ribozymes, viral RNA, and RNA-protein and DNA-protein complexes. This technology has significantly facilitated studies of macromolecular functions and mechanisms at the atomic level. Heavy atom derivatization for phase determination, a limiting factor in nucleic acid X-ray crystallography, however, has largely slowed down determination of new structures. In order to facilitate phase and structure determination using the powerful Multiwavelength Anomalous Dispersion (MAD) technique, we have recently demonstrated the chemical strategies of oxygen replacement with selenium in nucleic acids. We will present here enzymatic strategies to incorporate selenium into DNAs and RNAs by replacing the phosphate non-bridging oxygen atoms and substituting the exo-4-oxygen atoms on pyrimidines.

This work is supported by NIH (GM069703) and NSF (0521553).