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RNA Ligase Structures Reveal the Basis for RNA Specificity and Conformational Changes that Drive Ligation Forward

By Jayakrishnan Nandakumar, Stewart Shuman and Christopher D. Lima

Abstract

SummaryT4 RNA ligase 2 (Rnl2) and kinetoplastid RNA editing ligases exemplify a family of RNA repair enzymes that seal 3′OH/5′PO4 nicks in duplex RNAs via ligase adenylylation (step 1), AMP transfer to the nick 5′PO4 (step 2), and attack by the nick 3′OH on the 5′-adenylylated strand to form a phosphodiester (step 3). Crystal structures are reported for Rnl2 at discrete steps along this pathway: the covalent Rnl2-AMP intermediate; Rnl2 bound to an adenylylated nicked duplex, captured immediately following step 2; and Rnl2 at an adenylylated nick in a state poised for step 3. These structures illuminate the stereochemistry of nucleotidyl transfer and reveal how remodeling of active-site contacts and conformational changes propel the ligation reaction forward. Mutational analysis and comparison of nick-bound structures of Rnl2 and human DNA ligase I highlight common and divergent themes of substrate recognition that can explain their specialization for RNA versus DNA repair

Publisher: Elsevier Inc.
Year: 2006
DOI identifier: 10.1016/j.cell.2006.08.038
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