7kun

2'-F modification at 3' end of RNA primer complex with guanosine dinucleotide ligand G(5')ppp(5')G

spinqualitylabelsall models 7kun, resolution 1.58Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.58Å Ligands: GF2, GP3, LCC, LCG, LKC, MG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed The template-directed synthesis of RNA played an important role in the transition from prebiotic chemistry to the beginnings of RNA based life, but the mechanism of RNA copying chemistry is incompletely understood. We measured the kinetics of template copying with a set of primers with modified 3'-nucleotides and determined the crystal structures of these modified nucleotides in the context of a primer/template/substrate-analog complex. pH-rate profiles and solvent isotope effects show that deprotonation of the primer 3'-hydroxyl occurs prior to the rate limiting step, the attack of the alkoxide on the activated phosphate of the incoming nucleotide. The analogs with a 3 E ribose conformation show the fastest formation of 3'-5' phosphodiester bonds. Among those derivatives, the reaction rate is strongly correlated with the electronegativity of the 2'-substituent. We interpret our results in terms of differences in steric bulk and charge distribution in the ground vs. transition states. Structure-activity relationships in nonenzymatic template-directed RNA synthesis.,Giurgiu C, Fang Z, Aitken HRM, Kim SC, Pazienza L, Mittal S, Szostak JW Angew Chem Int Ed Engl. 2021 Aug 24. doi: 10.1002/anie.202109714. PMID:34428345 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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