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| | ==Topoisomerase VI-B bound to radicicol== | | ==Topoisomerase VI-B bound to radicicol== |
| - | <StructureSection load='2hkj' size='340' side='right' caption='[[2hkj]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='2hkj' size='340' side='right'caption='[[2hkj]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2hkj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/'saccharolobus_shibatae' 'saccharolobus shibatae']. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2HKJ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2hkj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharolobus_shibatae Saccharolobus shibatae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2HKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2HKJ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RDC:RADICICOL'>RDC</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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1mu5|1mu5]], [[1mx0|1mx0]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=RDC:RADICICOL'>RDC</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">top6B ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=2286 'Saccharolobus shibatae'])</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=2hkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hkj OCA], [https://pdbe.org/2hkj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2hkj RCSB], [https://www.ebi.ac.uk/pdbsum/2hkj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2hkj ProSAT]</span></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_(ATP-hydrolyzing) DNA topoisomerase (ATP-hydrolyzing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.3 5.99.1.3] </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=2hkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hkj OCA], [http://pdbe.org/2hkj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2hkj RCSB], [http://www.ebi.ac.uk/pdbsum/2hkj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2hkj ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TOP6B_SULSH TOP6B_SULSH]] Relaxes both positive and negative superturns and exhibits a strong decatenase activity.[HAMAP-Rule:MF_00322] | + | [https://www.uniprot.org/uniprot/TOP6B_SACSH TOP6B_SACSH] Relaxes both positive and negative supercoils and exhibits a strong decatenase and unknotting activity; it cannot introduce DNA supercoils (PubMed:7961685). ATP is absolutely required for DNA cleavage; the nonhydrolyzable analog AMP-PNP generates nicked or linear products from a supercoiled dsDNA substrate. Generates staggered two-nucleotide long 5' overhangs. The enzyme is covalently attached transiently to the 5'-ends of the cleaved strands (PubMed:11485995).<ref>PMID:11485995</ref> <ref>PMID:7961685</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Topoisomerase|Topoisomerase]] | + | *[[Topoisomerase 3D structures|Topoisomerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Saccharolobus shibatae]] | | [[Category: Saccharolobus shibatae]] |
| - | [[Category: Berger, J M]] | + | [[Category: Berger JM]] |
| - | [[Category: Corbett, K D]] | + | [[Category: Corbett KD]] |
| - | [[Category: Drug complex]]
| + | |
| - | [[Category: Ghkl]]
| + | |
| - | [[Category: Isomerase]]
| + | |
| - | [[Category: Radicicol]]
| + | |
| - | [[Category: Topoisomerase]]
| + | |
| Structural highlights
Function
TOP6B_SACSH Relaxes both positive and negative supercoils and exhibits a strong decatenase and unknotting activity; it cannot introduce DNA supercoils (PubMed:7961685). ATP is absolutely required for DNA cleavage; the nonhydrolyzable analog AMP-PNP generates nicked or linear products from a supercoiled dsDNA substrate. Generates staggered two-nucleotide long 5' overhangs. The enzyme is covalently attached transiently to the 5'-ends of the cleaved strands (PubMed:11485995).[1] [2]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Members of the GHL ATPase superfamily, including type II topoisomerases, Hsp90-class chaperones, and MutL, all share a common GHKL-type ATP-binding fold and act as nucleotide-controlled 'molecular clamps'. These enzymes' ATP-binding sites have proven to be rich drug targets, and certain inhibitors of type II topoisomerases and Hsp90 bind to this region and competitively inhibit these enzymes. Recently, it was found that radicicol, a drug known to block Hsp90 function, also inhibits the archaeal type IIB topoisomerase topo VI. Here, we use X-ray crystallography to show that despite low sequence identity ( approximately 10-12%) between topo VI and Hsp90, radicicol binds to the ATPase sites of these two enzymes in an equivalent manner. We further demonstrate that radicicol inhibits both the dimerization of the topo VI ATPase domains and ATP hydrolysis, two critical steps in the enzyme's strand passage reaction. This work contributes to a growing set of structures detailing the interactions between GHL-family proteins and various drugs, and reveals radicicol as a versatile scaffold for targeting distantly related GHL enzymes.
Structural basis for topoisomerase VI inhibition by the anti-Hsp90 drug radicicol.,Corbett KD, Berger JM Nucleic Acids Res. 2006;34(15):4269-77. Epub 2006 Aug 18. PMID:16920739[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Buhler C, Lebbink JH, Bocs C, Ladenstein R, Forterre P. DNA topoisomerase VI generates ATP-dependent double-strand breaks with two-nucleotide overhangs. J Biol Chem. 2001 Oct 5;276(40):37215-22. PMID:11485995 doi:10.1074/jbc.M101823200
- ↑ Bergerat A, Gadelle D, Forterre P. Purification of a DNA topoisomerase II from the hyperthermophilic archaeon Sulfolobus shibatae. A thermostable enzyme with both bacterial and eucaryal features. J Biol Chem. 1994 Nov 4;269(44):27663-9 PMID:7961685
- ↑ Corbett KD, Berger JM. Structural basis for topoisomerase VI inhibition by the anti-Hsp90 drug radicicol. Nucleic Acids Res. 2006;34(15):4269-77. Epub 2006 Aug 18. PMID:16920739 doi:10.1093/nar/gkl567
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