6U8U

RNA duplex bound with TNA 3'-3' imidazolium dimer

Summary for 6U8U

• Entry DOI: 10.2210/pdb6u8u/pdb
• Descriptor: RNA (5'-R(*(LCC)P*(LCC)P*(LCC)P*(LCG)P*AP*CP*UP*UP*AP*AP*GP*UP*CP*G)-3'), MAGNESIUM ION, 2-amino-3-[(R)-{[(3S,4R,5R)-5-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-4-hydroxyoxolan-3-yl]oxy}(hydroxy)phosphoryl]-1-[(S)-{[(3S,4R,5R)-5-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-4-hydroxyoxolan-3-yl]oxy}(hydroxy)phosphoryl]-1H-imidazol-3-ium, ... (4 entities in total)
• Functional Keywords: rna
• Biological source: synthetic construct
• Total number of polymer chains: 2
• Total formula weight: 10503.14

Authors

Szostak, J.W.,Zhang, W. (deposition date: 2019-09-05, release date: 2020-12-09, Last modification date: 2023-10-11)

Primary citation

Zhang, W.,Kim, S.C.,Tam, C.P.,Lelyveld, V.S.,Bala, S.,Chaput, J.C.,Szostak, J.W.
Structural interpretation of the effects of threo-nucleotides on nonenzymatic template-directed polymerization.
Nucleic Acids Res., 49:646-656, 2021

PubMed Abstract: The prebiotic synthesis of ribonucleotides is likely to have been accompanied by the synthesis of noncanonical nucleotides including the threo-nucleotide building blocks of TNA. Here, we examine the ability of activated threo-nucleotides to participate in nonenzymatic template-directed polymerization. We find that primer extension by multiple sequential threo-nucleotide monomers is strongly disfavored relative to ribo-nucleotides. Kinetic, NMR and crystallographic studies suggest that this is due in part to the slow formation of the imidazolium-bridged TNA dinucleotide intermediate in primer extension, and in part because of the greater distance between the attacking RNA primer 3'-hydroxyl and the phosphate of the incoming threo-nucleotide intermediate. Even a single activated threo-nucleotide in the presence of an activated downstream RNA oligonucleotide is added to the primer 10-fold more slowly than an activated ribonucleotide. In contrast, a single activated threo-nucleotide at the end of an RNA primer or in an RNA template results in only a modest decrease in the rate of primer extension, consistent with the minor and local structural distortions revealed by crystal structures. Our results are consistent with a model in which heterogeneous primordial oligonucleotides would, through cycles of replication, have given rise to increasingly homogeneous RNA strands.

PubMed: 33347562
DOI: 10.1093/nar/gkaa1215

Experimental method

X-RAY DIFFRACTION (2.4 Å)