1d9h

Structural origins of the exonuclease resistance of a zwitterionic RNA

spinqualitylabelsall models 1d9h, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1d9h is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: U31 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed Nuclease resistance and RNA affinity are key criteria in the search for optimal antisense nucleic acid modifications, but the origins of the various levels of resistance to nuclease degradation conferred by chemical modification of DNA and RNA are currently not understood. The 2'-O-aminopropyl (AP)-RNA modification displays the highest nuclease resistance among all phosphodiester-based analogues and its RNA binding affinity surpasses that of phosphorothioate DNA by 1 degrees C per modified residue. We found that oligodeoxynucleotides containing AP-RNA residues at their 3' ends competitively inhibit the degradation of single-stranded DNA by the Escherichia coli Klenow fragment (KF) 3'-5' exonuclease and snake venom phosphodiesterase. To shed light on the origins of nuclease resistance brought about by the AP modification, we determined the crystal structure of an A-form DNA duplex with AP-RNA modifications at 1.6-A resolution. In addition, the crystal structures of complexes between short DNA fragments carrying AP-RNA modifications and wild-type KF were determined at resolutions between 2.2 and 3.0 A and compared with the structure of the complex between oligo(dT) and the D355A/E357A KF mutant. The structural models suggest that interference of the positively charged 2'-O-substituent with the metal ion binding site B of the exonuclease allows AP-RNA to effectively slow down degradation. Structural origins of the exonuclease resistance of a zwitterionic RNA.,Teplova M, Wallace ST, Tereshko V, Minasov G, Symons AM, Cook PD, Manoharan M, Egli M Proc Natl Acad Sci U S A. 1999 Dec 7;96(25):14240-5. PMID:10588690 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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