4F1H: Crystal Structure Of Tdp2 From Danio Rerio Complexed With A Single Strand Dna

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.
PDB ID: 4F1HDownload
MMDB ID: 104537
PDB Deposition Date: 2012/5/6
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 1.66  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4F1H: trimeric; determined by author and by software (PISA)
Molecular Components in 4F1H
Label Count Molecule
Proteins (2 molecules)
Tyrosyl-dna Phosphodiesterase 2(Gene symbol: tdp2b)
Molecule annotation
Tyrosyl-dna Phosphodiesterase 2(Gene symbol: tdp2b)
Molecule annotation
Nucleotide(1 molecule)
DNA (5'-d(p*tp*gp*cp*ap*g)-3')
Molecule annotation
Chemicals (6 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB