2H7G

Structure of variola topoisomerase non-covalently bound to DNA

Summary for 2H7G

• Entry DOI: 10.2210/pdb2h7g/pdb
• Related: 2H7F
• Descriptor: 5'-D(*TP*TP*GP*TP*CP*GP*CP*CP*CP*TP*TP*A)-3', 5'-D(*TP*AP*AP*TP*AP*AP*GP*GP*GP*CP*GP*AP*CP*A)-3', DNA topoisomerase 1, ... (4 entities in total)
• Functional Keywords: type ib topoisomerase, dna binding, protein-dna complex, isomerase, isomerase-dna complex, isomerase/dna
• Biological source: Variola virus
• Total number of polymer chains: 3
• Total formula weight: 44559.66

Authors

Perry, K.,Hwang, Y.,Bushman, F.D.,Van Duyne, G.D. (deposition date: 2006-06-02, release date: 2006-08-15, Last modification date: 2024-02-14)

Primary citation

Perry, K.,Hwang, Y.,Bushman, F.D.,Van Duyne, G.D.
Structural basis for specificity in the poxvirus topoisomerase.
Mol.Cell, 23:343-354, 2006

PubMed Abstract: 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.

PubMed: 16885024
DOI: 10.1016/j.molcel.2006.06.015

Experimental method

X-RAY DIFFRACTION (1.9 Å)