1A31

HUMAN RECONSTITUTED DNA TOPOISOMERASE I IN COVALENT COMPLEX WITH A 22 BASE PAIR DNA DUPLEX

Summary for 1A31

• Entry DOI: 10.2210/pdb1a31/pdb
• Descriptor: DNA (5'-D(*AP*AP*AP*AP*AP*GP*AP*CP*5IUP*5IU*TP*GP*AP*AP*AP*AP*AP*5IUP*5IUP*5IUP*5IUP*T)-3'), DNA (5'-D(*AP*AP*AP*AP*AP*TP*5IUP*5IUP*5IUP*5IUP*CP*AP*AP*AP*GP*TP*CP*TP*TP*TP*TP*T)-3'), PROTEIN (TOPOISOMERASE I), ... (4 entities in total)
• Functional Keywords: topoisomerase i/dna, dna, topoisomerase i, isomerase-dna complex, isomerase/dna
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus, nucleolus :
• Total number of polymer chains: 3
• Total formula weight: 84733.38

Authors

Redinbo, M.R.,Stewart, L.,Kuhn, P.,Champoux, J.J.,Hol, W.G.J. (deposition date: 1998-01-27, release date: 1998-08-28, Last modification date: 2024-10-09)

Primary citation

Redinbo, M.R.,Stewart, L.,Kuhn, P.,Champoux, J.J.,Hol, W.G.
Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA.
Science, 279:1504-1513, 1998

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.

PubMed: 9488644
DOI: 10.1126/science.279.5356.1504

Experimental method

X-RAY DIFFRACTION (2.1 Å)