2m58

Structure of 2'-5' AG1 lariat forming ribozyme in its inactive state

spinqualitylabelsall models 2m58 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2m58 is a 1 chain structure with sequence from Synthetic construct. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Solution NMR Ligands: GTP Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed RNA-catalyzed lariat formation is present in both eukaryotes and prokaryotes. To date we lack structural insights into the catalytic mechanism of lariat-forming ribozymes. Here, we study an artificial 2'-5' AG1 lariat-forming ribozyme that shares the sequence specificity of lariat formation with the pre-mRNA splicing reaction. Using NMR, we solve the structure of the inactive state of the ribozyme in the absence of magnesium. The reaction center 5'-guanosine appears to be part of a helix with an exceptionally widened major groove, while the lariat-forming A48 is looped out at the apex of a pseudoknot. The model of the active state built by mutational analysis, molecular modeling, and small-angle X-ray scattering suggests that A48 is recognized by a conserved adenosine, juxtaposed to the 5'-guanosine in one base-pair step distance, while the G1-N7 coordinates a magnesium ion essential for the activation of the nucleophile. Our findings offer implications for lariat formation in RNA enzymes including the mechanism of the recognition of the branch-site adenosine. Structural principles of RNA catalysis in a 2'-5' lariat-forming ribozyme.,Carlomagno T, Amata I, Codutti L, Falb M, Fohrer J, Masiewicz P, Simon B J Am Chem Soc. 2013 Mar 20;135(11):4403-11. doi: 10.1021/ja311868t. Epub 2013 Mar, 8. PMID:23472843 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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