Crystal structure of a complex of a type IA DNA topoisomerase with a single-stranded DNA molecule

@article{Changela2001CrystalSO,
  title={Crystal structure of a complex of a type IA DNA topoisomerase with a single-stranded DNA molecule},
  author={Anita Changela and Russell J Digate and Alfonso Mondrag{\'o}n},
  journal={Nature},
  year={2001},
  volume={411},
  pages={1077-1081}
}
A variety of cellular processes, including DNA replication, transcription, and chromosome condensation, require enzymes that can regulate the ensuing topological changes occurring in DNA. Such enzymes—DNA topoisomerases—alter DNA topology by catalysing the cleavage of single-stranded DNA (ssDNA) or double-stranded DNA (dsDNA), the passage of DNA through the resulting break, and the rejoining of the broken phosphodiester backbone. DNA topoisomerase III from Escherichia coli belongs to the type… 

Crystal structure of a covalent intermediate in DNA cleavage and rejoining by Escherichia coli DNA topoisomerase I

Theructure of the covalent topoisomerase-DNA intermediate shows distinct conformational changes from the structure of the enzyme without bound DNA and provides detailed understanding of thecovalent catalysis required for strand cleavage to take place.

Type IA DNA topoisomerases: Strictly one step at a time

  • J. Champoux
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 2002
The experiments described by Dekker et al. provide an elegant and convincing test of a model of what happens after cleavage to effect the strand passage reaction has long fascinated investigators working on the type I enzymes.

Control of Strand Scission by Type IIA Topoisomerases

This dissertation helps to explain years of biochemical studies, unifies many elements of topo II mechanism and its control by allostery, and has implications for both understanding large ATP-dependent DNA-remodeling molecular machines as a whole, as well as understanding the means by which small molecules target these enzymes for clinical benefit.

Flexibility at Gly-194 Is Required for DNA Cleavage and Relaxation Activity of Escherichia coli DNA Topoisomerase I*

Site-directed mutagenesis of the strictly conserved Gly-194 at the N terminus of this α helix in Escherichia coli DNA topoisomerase I showed that flexibility around this glycine residue is required for DNA cleavage and relaxation activity and supports a functional role for this hinge region in the enzyme conformational change.

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

The structure of a complex between the DNA-binding and cleavage core of Saccharomyces cerevisiae Topo II and a gate-DNA segment is presented, revealing that the enzyme enforces a 150° DNA bend through a mechanism similar to that of remodelling proteins such as integration host factor.

Inhibition of type IA topoisomerase by a monoclonal antibody through perturbation of DNA cleavage–religation equilibrium

Monoclonal antibodies with such a mechanism of inhibition can serve as invaluable tools for probing the structure and mechanism of the enzyme, as well as in the design of novel inhibitors that arrest enzyme activity.

A novel and unified two-metal mechanism for DNA cleavage by type II and IA topoisomerases

The structure of the DNA-binding and cleavage core of Saccharomyces cerevisiae topoisomerase II covalently linked to DNA through its active-site tyrosine at 2.5 Å resolution is presented, revealing for the first time the organization of a cleavage-competent type II topoisomersase configuration.

Site-directed Mutagenesis of Residues Involved in G Strand DNA Binding by Escherichia coli DNA Topoisomerase I*

Site-directed mutagenesis experiments show that the side chains of Arg-195 and Gln-197 are required for DNA cleavage by the enzyme and are likely to be important for positioning of the G strand of DNA at the active site prior toDNA cleavage.
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