Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA.
Article Details
- CitationCopy to clipboard
Redinbo MR, Stewart L, Kuhn P, Champoux JJ, Hol WG
Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA.
Science. 1998 Mar 6;279(5356):1504-13.
- PubMed ID
- 9488644 [ View in PubMed]
- Abstract
Topoisomerases I promote the relaxation of DNA superhelical tension by introducing a transient single-stranded break in duplex DNA and are vital for the processes of replication, transcription, and recombination. The crystal structures at 2.1 and 2.5 angstrom resolution of reconstituted human topoisomerase I comprising the core and carboxyl-terminal domains in covalent and noncovalent complexes with 22-base pair DNA duplexes reveal an enzyme that "clamps" around essentially B-form DNA. The core domain and the first eight residues of the carboxyl-terminal domain of the enzyme, including the active-site nucleophile tyrosine-723, share significant structural similarity with the bacteriophage family of DNA integrases. A binding mode for the anticancer drug camptothecin is proposed on the basis of chemical and biochemical information combined with these three-dimensional structures of topoisomerase I-DNA complexes.