Talk abstracts
Talk on Friday 03:45-04:00pm submitted by Evan Cramer
Crystal Structure of the RNA Cleaving 10-23 DNAzyme Captured in a Pre-Catalytic State
Evan Cramer (Department of Biochemistry, West Virginia University), Sarah Starcovic (Department of Biochemistry, West Virginia University), Aaron Robart (Department of Biochemistry, West Virginia University)
Abstract:
Deoxyribozymes (DNAzymes) are short single-stranded DNA sequences capable of catalyzing chemical reactions such as RNA cleavage, thymine excision, RNA/DNA ligation, and thymine dimer resolution. Among these, RNA cleaving DNAzymes have emerged as the most prominent due to their applications in medicine as potential protein expression knockdown therapeutics and antiviral agents; however, the lack of a structural insight into catalysis hinders further optimization. Here, we report a structure of the RNA cleaving 10-23 DNAzyme, which requires magnesium as a cofactor. In crystallo, the DNAzyme forms a dimer mediated primarily through a palindromic sequence within the catalytic core. The substrate adopts a sharp kink at the cleavage site that exposes the scissile phosphate with magnesium ions coordinated. This structure reveals that the 10-23 DNAzyme appears to function similarly to RNA cleaving ribozymes such as Group II Introns and functions by inducing a strained substrate conformation that allows the cofactor to interact with the consensus site.
Keywords: DNAzyme, X-Ray Crystallography, RNA Cleavage