8E2S

Crystal structure of TadAC-1.19

8E2S の概要

• エントリーDOI: 10.2210/pdb8e2s/pdb
• 分子名称: tRNA-specific adenosine deaminase 1.19, ZINC ION (3 entities in total)
• 機能のキーワード: deaminase, tadac, dna binding protein
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 149855.71

構造登録者

Feliciano, P.R.,Lee, S.J.,Ciaramella, G. (登録日: 2022-08-15, 公開日: 2023-01-11, 最終更新日: 2023-10-25)

主引用文献

Lam, D.K.,Feliciano, P.R.,Arif, A.,Bohnuud, T.,Fernandez, T.P.,Gehrke, J.M.,Grayson, P.,Lee, K.D.,Ortega, M.A.,Sawyer, C.,Schwaegerle, N.D.,Peraro, L.,Young, L.,Lee, S.J.,Ciaramella, G.,Gaudelli, N.M.
Improved cytosine base editors generated from TadA variants.
Nat.Biotechnol., 41:686-697, 2023

PubMed Abstract: Cytosine base editors (CBEs) enable programmable genomic C·G-to-T·A transition mutations and typically comprise a modified CRISPR-Cas enzyme, a naturally occurring cytidine deaminase, and an inhibitor of uracil repair. Previous studies have shown that CBEs utilizing naturally occurring cytidine deaminases may cause unguided, genome-wide cytosine deamination. While improved CBEs that decrease stochastic genome-wide off-targets have subsequently been reported, these editors can suffer from suboptimal on-target performance. Here, we report the generation and characterization of CBEs that use engineered variants of TadA (CBE-T) that enable high on-target C·G to T·A across a sequence-diverse set of genomic loci, demonstrate robust activity in primary cells and cause no detectable elevation in genome-wide mutation. Additionally, we report cytosine and adenine base editors (CABEs) catalyzing both A-to-I and C-to-U editing (CABE-Ts). Together with ABEs, CBE-Ts and CABE-Ts enable the programmable installation of all transition mutations using laboratory-evolved TadA variants with improved properties relative to previously reported CBEs.

PubMed: 36624149
DOI: 10.1038/s41587-022-01611-9

実験手法

X-RAY DIFFRACTION (2.95 Å)