270912 Unraveling the Mechanism of a DNA Nanotechnology: The 10-23 Dnazyme

Tuesday, October 30, 2012: 1:35 PM
Pennsylvania East (Westin )
Margaret C. Linak and Kevin D. Dorfman, Chemical Engineering and Materials Science, University of Minnesota, Minneapolis, MN

Many emerging DNA nanotechnologies are difficult or even impossible to crystallize, frustrating attempts to connect their structure and function.  Using a straightforward multi-scale simulation approach, we developed an atomic scale model of one such nanotechnology that has resisted attempts at crystallization, the widely used 10-23 DNAzyme.  Deoxyribozymes (DNAzymes) are a new class of small catalytic oligodeoxynucleotides composed entirely of DNA.  The 10-23 DNAzyme consists of a conserved 15-base catalytic core that is flanked by binding arms typically 7-10 bases in length with sequence complementary to a target single-stranded RNA molecule.  The 10-23 DNAzyme is capable of cleaving at a purine-pyrimidine junction with both high turnover rate and substrate affinity.  The ability of the 10-23 DNAzyme to cleave an RNA substrate has lead to both in vitro and in vivo applications although the evidence for its biochemical activity remains indirect.  Our simulations suggest a plausible mechanism for the catalysis of RNA cleavage by this single-stranded DNA molecule.  Two critical structural features were found:  (i) the unstacking and rotation of the RNA nucleotide at the cleavage site, and (ii) the formation of electrostatic traps for cofactor metal ions.  

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