4GZ2: Mus Musculus Tdp2 Excluded Ssdna Complex

Citation:
Abstract
The topoisomerase II (topo II) DNA incision-and-ligation cycle can be poisoned (for example following treatment with cancer chemotherapeutics) to generate cytotoxic DNA double-strand breaks (DSBs) with topo II covalently conjugated to DNA. Tyrosyl-DNA phosphodiesterase 2 (Tdp2) protects genomic integrity by reversing 5'-phosphotyrosyl-linked topo II-DNA adducts. Here, X-ray structures of mouse Tdp2-DNA complexes reveal that Tdp2 beta-2-helix-beta DNA damage-binding 'grasp', helical 'cap' and DNA lesion-binding elements fuse to form an elongated protein-DNA conjugate substrate-interaction groove. The Tdp2 DNA-binding surface is highly tailored for engagement of 5'-adducted single-stranded DNA ends and restricts nonspecific endonucleolytic or exonucleolytic processing. Structural, mutational and functional analyses support a single-metal ion catalytic mechanism for the exonuclease-endonuclease-phosphatase (EEP) nuclease superfamily and establish a molecular framework for targeted small-molecule blockade of Tdp2-mediated resistance to anticancer topoisomerase drugs.
PDB ID: 4GZ2Download
MMDB ID: 104627
PDB Deposition Date: 2012/9/5
Updated in MMDB: 2012/12
Experimental Method:
x-ray diffraction
Resolution: 1.85  Å
Source Organism:
synthetic construct
Similar Structures:
Biological Unit for 4GZ2: dimeric; determined by author and by software (PISA)
Molecular Components in 4GZ2
Label Count Molecule
Protein (1 molecule)
1
Tyrosyl-dna Phosphodiesterase 2(Gene symbol: Tdp2)
Molecule annotation
Nucleotide(1 molecule)
1
DNA (5'-d(*cp*ap*tp*cp*cp*gp*ap*ap*tp*tp*cp*g)-3')
Molecule annotation
Chemicals (2 molecules)
1
1
2
1
* Click molecule labels to explore molecular sequence information.

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