Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA

Journal Article · Fri Mar 06 04:00:00 EST 1998 · Science

DOI:https://doi.org/10.1126/science.279.5356.1504· OSTI ID:621404

Redinbo, M R; Stewart, L ^[1]; Kuhn, P ^[2]

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1. Univ. of Washington, Seattle, WA (United States)
2. Stanford Synchrotron Radiation Lab., CA (United States); and others

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 comptothecin is proposed on the basis of chemical and biochemical information combined with these three-dimensional structures of topoisomerase I-DNA complexes. 62 refs., 6 figs.

• OSTI ID: 621404
• Journal Information: Science, Journal Name: Science Journal Issue: 5356 Vol. 279; ISSN SCIEAS; ISSN 0036-8075
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
CRYSTAL STRUCTURE
DNA REPLICATION
ENZYMES
ISOMERASES
MAN
TRANSCRIPTION