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| | ==Crystal structure of full-length E.Coli topoisomerase I in complex with ssDNA== | | ==Crystal structure of full-length E.Coli topoisomerase I in complex with ssDNA== |
| - | <StructureSection load='4rul' size='340' side='right' caption='[[4rul]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='4rul' size='340' side='right'caption='[[4rul]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4rul]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RUL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RUL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4rul]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_DH1 Escherichia coli DH1] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RUL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RUL FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pwt|3pwt]], [[3px7|3px7]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_topoisomerase DNA topoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.2 5.99.1.2] </span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4rul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rul OCA], [https://pdbe.org/4rul PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rul RCSB], [https://www.ebi.ac.uk/pdbsum/4rul PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rul ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4rul FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rul OCA], [http://pdbe.org/4rul PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4rul RCSB], [http://www.ebi.ac.uk/pdbsum/4rul PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/C9QXS7_ECOD1 C9QXS7_ECOD1]] 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.[HAMAP-Rule:MF_00952][SAAS:SAAS00003469] | + | [https://www.uniprot.org/uniprot/TOP1_ECOLI TOP1_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.<ref>PMID:9497321</ref> <ref>PMID:10681504</ref> <ref>PMID:21482796</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4rul" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4rul" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Topoisomerase 3D structures|Topoisomerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: DNA topoisomerase]] | + | [[Category: Escherichia coli DH1]] |
| - | [[Category: Chen, B]] | + | [[Category: Large Structures]] |
| - | [[Category: Tan, K]] | + | [[Category: Synthetic construct]] |
| - | [[Category: Tse-Dinh, Y C]] | + | [[Category: Chen B]] |
| - | [[Category: Isomerase-dna complex]] | + | [[Category: Tan K]] |
| - | [[Category: Topoisomerase 1a]] | + | [[Category: Tse-Dinh YC]] |
| Structural highlights
Function
TOP1_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 PubMed
Escherichia 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 Also
References
- ↑ Chen SJ, Wang JC. Identification of active site residues in Escherichia coli DNA topoisomerase I. J Biol Chem. 1998 Mar 13;273(11):6050-6. PMID:9497321
- ↑ Zhu CX, Tse-Dinh YC. The acidic triad conserved in type IA DNA topoisomerases is required for binding of Mg(II) and subsequent conformational change. J Biol Chem. 2000 Feb 25;275(8):5318-22. PMID:10681504
- ↑ Zhang Z, Cheng B, Tse-Dinh YC. Crystal structure of a covalent intermediate in DNA cleavage and rejoining by Escherichia coli DNA topoisomerase I. Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):6939-44. Epub 2011 Apr 11. PMID:21482796 doi:http://dx.doi.org/10.1073/pnas.1100300108
- ↑ Tan K, Zhou Q, Cheng B, Zhang Z, Joachimiak A, Tse-Dinh YC. Structural basis for suppression of hypernegative DNA supercoiling by E. coli topoisomerase I. Nucleic Acids Res. 2015 Dec 15;43(22):11031-46. doi: 10.1093/nar/gkv1073. Epub, 2015 Oct 20. PMID:26490962 doi:http://dx.doi.org/10.1093/nar/gkv1073
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