5CKK

Crystal structure of 9DB1* deoxyribozyme

5CKK の概要

• エントリーDOI: 10.2210/pdb5ckk/pdb
• 分子名称: DNA (44-MER), RNA (5'-R(P*GP*CP*AP*CP*UP*AP*GP*AP*UP*CP*GP*GP*AP*UP*G)-3'), MAGNESIUM ION (3 entities in total)
• 機能のキーワード: deoxyribozyme, rna-ligase, catalytic dna, ligase
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18556.59

構造登録者

Ponce-Salvatierra, A.,Hoebartner, C.,Pena, V. (登録日: 2015-07-15, 公開日: 2016-01-13, 最終更新日: 2024-01-10)

主引用文献

Ponce-Salvatierra, A.,Wawrzyniak-Turek, K.,Steuerwald, U.,Hobartner, C.,Pena, V.
Crystal structure of a DNA catalyst.
Nature, 529:231-234, 2016

PubMed Abstract: Catalysis in biology is restricted to RNA (ribozymes) and protein enzymes, but synthetic biomolecular catalysts can also be made of DNA (deoxyribozymes) or synthetic genetic polymers. In vitro selection from synthetic random DNA libraries identified DNA catalysts for various chemical reactions beyond RNA backbone cleavage. DNA-catalysed reactions include RNA and DNA ligation in various topologies, hydrolytic cleavage and photorepair of DNA, as well as reactions of peptides and small molecules. In spite of comprehensive biochemical studies of DNA catalysts for two decades, fundamental mechanistic understanding of their function is lacking in the absence of three-dimensional models at atomic resolution. Early attempts to solve the crystal structure of an RNA-cleaving deoxyribozyme resulted in a catalytically irrelevant nucleic acid fold. Here we report the crystal structure of the RNA-ligating deoxyribozyme 9DB1 (ref. 14) at 2.8 Å resolution. The structure captures the ligation reaction in the post-catalytic state, revealing a compact folding unit stabilized by numerous tertiary interactions, and an unanticipated organization of the catalytic centre. Structure-guided mutagenesis provided insights into the basis for regioselectivity of the ligation reaction and allowed remarkable manipulation of substrate recognition and reaction rate. Moreover, the structure highlights how the specific properties of deoxyribose are reflected in the backbone conformation of the DNA catalyst, in support of its intricate three-dimensional organization. The structural principles underlying the catalytic ability of DNA elucidate differences and similarities in DNA versus RNA catalysts, which is relevant for comprehending the privileged position of folded RNA in the prebiotic world and in current organisms.

PubMed: 26735012
DOI: 10.1038/nature16471

実験手法

X-RAY DIFFRACTION (2.801 Å)