Structural basis for gate-DNA recognition and bending by type IIA topoisomerases

Nature. 2007 Dec 20;450(7173):1201-5. doi: 10.1038/nature06396.

Abstract

Type II topoisomerases disentangle DNA to facilitate chromosome segregation, and represent a major class of therapeutic targets. Although these enzymes have been studied extensively, a molecular understanding of DNA binding has been lacking. Here we present the structure of a complex between the DNA-binding and cleavage core of Saccharomyces cerevisiae Topo II (also known as Top2) and a gate-DNA segment. The structure reveals that the enzyme enforces a 150 degrees DNA bend through a mechanism similar to that of remodelling proteins such as integration host factor. Large protein conformational changes accompany DNA deformation, creating a bipartite catalytic site that positions the DNA backbone near a reactive tyrosine and a coordinated magnesium ion. This configuration closely resembles the catalytic site of type IA topoisomerases, reinforcing an evolutionary link between these structurally and functionally distinct enzymes. Binding of DNA facilitates opening of an enzyme dimerization interface, providing visual evidence for a key step in DNA transport.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding Sites
  • Catalysis
  • DNA / chemistry*
  • DNA / metabolism*
  • DNA Topoisomerases, Type II / chemistry*
  • DNA Topoisomerases, Type II / metabolism*
  • Dimerization
  • Models, Molecular
  • Nucleic Acid Conformation
  • Protein Conformation
  • Saccharomyces cerevisiae / enzymology*
  • Structure-Activity Relationship

Substances

  • DNA
  • DNA Topoisomerases, Type II

Associated data

  • PDB/2RGR