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Research ArticlesThe Structural Basis of Ribozyme-Catalyzed RNA AssemblyLife originated, according to the RNA World hypothesis, from self-replicating ribozymes that catalyzed ligation of RNA fragments. We have solved the 2.6 angstrom crystal structure of a ligase ribozyme that catalyzes regiospecific formation of a 5' to 3' phosphodiester bond between the 5'-triphosphate and the 3'-hydroxyl termini of two RNA fragments. Invariant residues form tertiary contacts that stabilize a flexible stem of the ribozyme at the ligation site, where an essential magnesium ion coordinates three phosphates. The structure of the active site permits us to suggest how transition-state stabilization and a general base may catalyze the ligation reaction required for prebiotic RNA assembly. The Center for the Molecular Biology of RNA and Department of Chemistry and Biochemistry, Robert L. Sinsheimer Laboratories, University of California, Santa Cruz, Santa Cruz, CA 95064, USA. * To whom correspondence should be addressed. E-mail: wgscott{at}chemistry.ucsc.edu
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