2H7G: Structure Of Variola Topoisomerase Non-covalently Bound To Dna

Although smallpox has been eradicated from the human population, it is presently feared as a possible agent of bioterrorism. The smallpox virus codes for its own topoisomerase enzyme that differs from its cellular counterpart by requiring a specific DNA sequence for activation of catalysis. Here we present crystal structures of the smallpox virus topoisomerase enzyme bound both covalently and noncovalently to a specific DNA sequence. These structures reveal the basis for site-specific DNA recognition, and they explain how catalysis is likely activated by formation of a specific enzyme-DNA interface. Unexpectedly, the poxvirus enzyme uses a major groove binding alpha helix that is not present in the human enzyme to recognize part of the core recognition sequence and activate the enzyme for catalysis. The topoisomerase-DNA complex structures also provide a three-dimensional framework that may facilitate the rational design of therapeutic agents to treat poxvirus infections.
PDB ID: 2H7GDownload
MMDB ID: 74665
PDB Deposition Date: 2006/6/2
Updated in MMDB: 2017/10
Experimental Method:
x-ray diffraction
Resolution: 1.9  Å
Source Organism:
Variola virus
Similar Structures:
Biological Unit for 2H7G: trimeric; determined by author
Molecular Components in 2H7G
Label Count Molecule
Protein (1 molecule)
DNA Topoisomerase 1(Gene symbol: I6R)
Molecule annotation
Nucleotides(2 molecules)
Molecule annotation
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB