4gfh
From Proteopedia
Topoisomerase II-DNA-AMPPNP complex
Structural highlights
FunctionTOP2_YEAST Control of topological states of DNA by transient breakage and subsequent rejoining of DNA strands. Topoisomerase II makes double-strand breaks. Essential during mitosis and meiosis for proper segregation of daughter chromosomes.[1] [2] Publication Abstract from PubMedType IIA topoisomerases control DNA supercoiling and disentangle chromosomes through a complex ATP-dependent strand-passage mechanism. Although a general framework exists for type IIA topoisomerase function, the architecture of the full-length enzyme has remained undefined. Here we present the structure of a fully catalytic Saccharomyces cerevisiae topoisomerase II homodimer complexed with DNA and a nonhydrolyzable ATP analog. The enzyme adopts a domain-swapped configuration wherein the ATPase domain of one protomer sits atop the nucleolytic region of its partner subunit. This organization produces an unexpected interaction between bound DNA and a conformational transducing element in the ATPase domain, which we show is critical for both DNA-stimulated ATP hydrolysis and global topoisomerase activity. Our data indicate that the ATPase domains pivot about each other to ensure unidirectional strand passage and that this state senses bound DNA to promote ATP turnover and enzyme reset. Structure of a topoisomerase II-DNA-nucleotide complex reveals a new control mechanism for ATPase activity.,Schmidt BH, Osheroff N, Berger JM Nat Struct Mol Biol. 2012 Nov;19(11):1147-54. doi: 10.1038/nsmb.2388. Epub 2012, Sep 30. PMID:23022727[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|