Structural insights into the function of type IB topoisomerases.
Topoisomerases relax the DNA superhelical tension that arises in cells as a result of several nuclear processes, including transcription, replication and recombination. Recently determined crystal structures of human topoisomerase I in complex with DNA and of the 27 kDa catalytic domain of the vaccinia virus topoisomerase have advanced our understanding of the eukaryotic type IB topoisomerases. These recent structural results provide insights into functional aspects of these topoisomerases, including their DNA binding, strand cleavage and religation activities, as well as the mechanism that these enzymes use to relax DNA superhelical tension. In addition, two proposed models of the anticancer drug camptothecin bound to a covalent complex of human topoisomerase I and DNA suggest a structural basis for the mode of action of the drug.
Department of Biological Structure and Biomolecular Structure Center, Howard Hughes Medical Institute, School of Medicine, University of Washington, Seattle, WA 98195, USA. redinbo@u.washington.edu
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Redinbo
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Champoux
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D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002166:Camptothecin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D004278:DNA, Superhelical / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D013379:Substrate Specificity; D014616:Vaccinia virus / Q000201:enzymology
D000972:Antineoplastic Agents, Phytogenic; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin