4FVA

Crystal structure of truncated Caenorhabditis elegans TDP2

4FVA の概要

• エントリーDOI: 10.2210/pdb4fva/pdb
• 関連するPDBエントリー: 4F1H 4F1I 4FPV 4GEW
• 分子名称: 5'-tyrosyl-DNA phosphodiesterase, 1,2-ETHANEDIOL, MAGNESIUM ION, ... (5 entities in total)
• 機能のキーワード: 5'-phosphotyrosyl-dna diesterase, hydrolase
• 由来する生物種: Caenorhabditis elegans (nematode)
• 細胞内の位置: Nucleus (By similarity): Q9XWG3
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 118796.57

構造登録者

Shi, K.,Kurahashi, K.,Aihara, H. (登録日: 2012-06-29, 公開日: 2012-10-31, 最終更新日: 2024-02-28)

主引用文献

Shi, K.,Kurahashi, K.,Gao, R.,Tsutakawa, S.E.,Tainer, J.A.,Pommier, Y.,Aihara, H.
Structural basis for recognition of 5'-phosphotyrosine adducts by Tdp2.
Nat.Struct.Mol.Biol., 19:1372-1377, 2012

PubMed Abstract: The DNA-repair enzyme Tdp2 resolves 5'-phosphotyrosyl DNA adducts and mediates resistance to anticancer drugs that target covalent topoisomerase-DNA complexes. Tdp2 also participates in key signaling pathways during development and tumorigenesis and cleaves a protein-RNA linkage during picornavirus replication. The crystal structure of zebrafish Tdp2 bound to DNA reveals a deep, narrow basic groove that selectively accommodates the 5' end of single-stranded DNA in a stretched conformation. The crystal structure of the full-length Caenorhabditis elegans Tdp2 shows that this groove can also accommodate an acidic peptide stretch in vitro, with glutamate and aspartate side chains occupying the DNA backbone phosphate-binding sites. This extensive molecular mimicry suggests a potential mechanism for autoregulation and interaction of Tdp2 with phosphorylated proteins in signaling. Our study provides a framework to interrogate functions of Tdp2 and develop inhibitors for chemotherapeutic and antiviral applications.

PubMed: 23104058
DOI: 10.1038/nsmb.2423

実験手法

X-RAY DIFFRACTION (2.07 Å)