4rul
Crystal structure of full-length E.Coli topoisomerase I in complex with ssDNA
Structural highlights
FunctionTOP1_ECOLI Releases the supercoiling and torsional tension of DNA, which is introduced during the DNA replication and transcription, by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand, thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone.[1] [2] [3] Publication Abstract from PubMedEscherichia coli topoisomerase I has an essential function in preventing hypernegative supercoiling of DNA. A full length structure of E. coli topoisomerase I reported here shows how the C-terminal domains bind single-stranded DNA (ssDNA) to recognize the accumulation of negative supercoils in duplex DNA. These C-terminal domains of E. coli topoisomerase I are known to interact with RNA polymerase, and two flexible linkers within the C-terminal domains may assist in the movement of the ssDNA for the rapid removal of transcription driven negative supercoils. The structure has also unveiled for the first time how the 4-Cys zinc ribbon domain and zinc ribbon-like domain bind ssDNA with primarily pi-stacking interactions. This novel structure, in combination with new biochemical data, provides important insights into the mechanism of genome regulation by type IA topoisomerases that is essential for life, as well as the structures of homologous type IA TOP3alpha and TOP3beta from higher eukaryotes that also have multiple 4-Cys zinc ribbon domains required for their physiological functions. Structural basis for suppression of hypernegative DNA supercoiling by E. coli topoisomerase I.,Tan K, Zhou Q, Cheng B, Zhang Z, Joachimiak A, Tse-Dinh YC Nucleic Acids Res. 2015 Dec 15;43(22):11031-46. doi: 10.1093/nar/gkv1073. Epub, 2015 Oct 20. PMID:26490962[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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