4F1H
Crystal structure of TDP2 from Danio rerio complexed with a single strand DNA
Summary for 4F1H
| Entry DOI | 10.2210/pdb4f1h/pdb |
| Related | 4F1I 4FPV 4FVA 4GEW |
| Descriptor | DNA (5'-D(P*TP*GP*CP*AP*G)-3'), Tyrosyl-DNA phosphodiesterase 2, PHOSPHATE ION, ... (7 entities in total) |
| Functional Keywords | 5'-tyrosyl dna phosphodiesterase, hydrolase-dna complex, hydrolase/dna |
| Biological source | Danio rerio (leopard danio,zebra danio,zebra fish) More |
| Cellular location | Nucleus (By similarity): Q5XJA0 Q5XJA0 |
| Total number of polymer chains | 3 |
| Total formula weight | 59106.25 |
| Authors | Shi, K.,Kurahashi, K.,Aihara, H. (deposition date: 2012-05-06, release date: 2012-10-31, Last modification date: 2024-02-28) |
| Primary citation | 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 Cited by 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: 23104058DOI: 10.1038/nsmb.2423 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.662 Å) |
Structure validation
Download full validation report
