4F1I

Crystal structure of SeMet TDP2 from Caenorhabditis elegans

Summary for 4F1I

• Entry DOI: 10.2210/pdb4f1i/pdb
• Related: 4F1H 4FPV 4FVA 4GEW
• Descriptor: 5'-tyrosyl-DNA phosphodiesterase, GLYCEROL (3 entities in total)
• Functional Keywords: 5'-tyrosyl dna phosphodiesterase, hydrolase
• Biological source: Caenorhabditis elegans (nematode)
• Cellular location: Nucleus : Q9XWG3
• Total number of polymer chains: 1
• Total formula weight: 42242.65

Authors

Shi, K.,Kurahashi, K.,Aihara, H. (deposition date: 2012-05-07, release date: 2012-10-31, Last modification date: 2024-11-06)

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

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)