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5mbv
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Cryo-EM structure of Lambda Phage protein GamS bound to RecBCD== | |
| + | <StructureSection load='5mbv' size='340' side='right' caption='[[5mbv]], [[Resolution|resolution]] 3.80Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5mbv]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MBV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MBV FirstGlance]. <br> | ||
| + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5ld2|5ld2]]</td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Exodeoxyribonuclease_V Exodeoxyribonuclease V], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.11.5 3.1.11.5] </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=5mbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mbv OCA], [http://pdbe.org/5mbv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mbv RCSB], [http://www.ebi.ac.uk/pdbsum/5mbv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mbv ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/GAM_LAMBD GAM_LAMBD]] Binds to host RecBCD nuclease and inhibits it thereby protecting the viral DNA against recBCD mediated degradation.<ref>PMID:17544443</ref> [[http://www.uniprot.org/uniprot/RECB_ECOLI RECB_ECOLI]] A helicase/nuclease that prepares dsDNA breaks (DSB) for recombinational DNA repair. Binds to DSBs and unwinds DNA via a rapid (>1 kb/second) and highly processive (>30 kb) ATP-dependent bidirectional helicase. Unwinds dsDNA until it encounters a Chi (crossover hotspot instigator, 5'-GCTGGTGG-3') sequence from the 3' direction. Cuts ssDNA a few nucleotides 3' to Chi site, by nicking one strand or switching the strand degraded (depending on the reaction conditions). The properties and activities of the enzyme are changed at Chi. The Chi-altered holoenzyme produces a long 3'-ssDNA overhang which facilitates RecA-binding to the ssDNA for homologous DNA recombination and repair. Holoenzyme degrades any linearized DNA that is unable to undergo homologous recombination (PubMed:4562392, PubMed:4552016, PubMed:123277). In the holoenzyme this subunit contributes ATPase, 3'-5' helicase, exonuclease activity and loads RecA onto ssDNA. The RecBC complex requires the RecD subunit for nuclease activity, but can translocate along ssDNA in both directions.<ref>PMID:10197988</ref> <ref>PMID:10518611</ref> <ref>PMID:10766864</ref> <ref>PMID:123277</ref> <ref>PMID:12815437</ref> <ref>PMID:12815438</ref> <ref>PMID:1535156</ref> <ref>PMID:16041061</ref> <ref>PMID:1618858</ref> <ref>PMID:16388588</ref> <ref>PMID:18079176</ref> <ref>PMID:20852646</ref> <ref>PMID:23851395</ref> <ref>PMID:25073102</ref> <ref>PMID:4268693</ref> <ref>PMID:4552016</ref> <ref>PMID:4562392</ref> <ref>PMID:7608206</ref> <ref>PMID:9192629</ref> <ref>PMID:9230304</ref> <ref>PMID:9448271</ref> <ref>PMID:9790841</ref> [[http://www.uniprot.org/uniprot/RECD_ECOLI RECD_ECOLI]] A helicase/nuclease that prepares dsDNA breaks (DSB) for recombinational DNA repair. Binds to DSBs and unwinds DNA via a rapid (>1 kb/second) and highly processive (>30 kb) ATP-dependent bidirectional helicase. Unwinds dsDNA until it encounters a Chi (crossover hotspot instigator, 5'-GCTGGTGG-3') sequence from the 3' direction. Cuts ssDNA a few nucleotides 3' to Chi site, by nicking one strand or switching the strand degraded (depending on the reaction conditions). The properties and activities of the enzyme are changed at Chi. The Chi-altered holoenzyme produces a long 3'-ssDNA overhang which facilitates RecA-binding to the ssDNA for homologous DNA recombination and repair. In the holoenzyme this subunit contributes ssDNA-dependent ATPase and fast 5'-3' helicase activity. When added to pre-assembled RecBC greatly stimulates nuclease activity and augments holoenzyme processivity. Negatively regulates the RecA-loading ability of RecBCD.<ref>PMID:10197988</ref> <ref>PMID:10840065</ref> <ref>PMID:12815437</ref> <ref>PMID:12815438</ref> <ref>PMID:1535156</ref> <ref>PMID:16041061</ref> <ref>PMID:1618858</ref> <ref>PMID:18079176</ref> <ref>PMID:23851395</ref> <ref>PMID:7608206</ref> <ref>PMID:9192629</ref> <ref>PMID:9230304</ref> <ref>PMID:9448271</ref> <ref>PMID:9790841</ref> [[http://www.uniprot.org/uniprot/RECC_ECOLI RECC_ECOLI]] A helicase/nuclease that prepares dsDNA breaks (DSB) for recombinational DNA repair. Binds to DSBs and unwinds DNA via a rapid (>1 kb/second) and highly processive (>30 kb) ATP-dependent bidirectional helicase. Unwinds dsDNA until it encounters a Chi (crossover hotspot instigator, 5'-GCTGGTGG-3') sequence from the 3' direction. Cuts ssDNA a few nucleotides 3' to Chi site, by nicking one strand or switching the strand degraded (depending on the reaction conditions). The properties and activities of the enzyme are changed at Chi. The Chi-altered holoenzyme produces a long 3'-ssDNA overhang which facilitates RecA-binding to the ssDNA for homologous DNA recombination and repair. Holoenzyme degrades any linearized DNA that is unable to undergo homologous recombination (PubMed:4562392, PubMed:4552016, PubMed:123277). In the holoenzyme this subunit almost certainly recognizes the wild-type Chi sequence, when added to isolated RecB increases its ATP-dependent helicase processivity. The RecBC complex requires the RecD subunit for nuclease activity, but can translocate along ssDNA in both directions.<ref>PMID:10197988</ref> <ref>PMID:10884344</ref> <ref>PMID:123277</ref> <ref>PMID:12815437</ref> <ref>PMID:12815438</ref> <ref>PMID:1535156</ref> <ref>PMID:16041061</ref> <ref>PMID:1618858</ref> <ref>PMID:20852646</ref> <ref>PMID:23851395</ref> <ref>PMID:4268693</ref> <ref>PMID:4552016</ref> <ref>PMID:4562392</ref> <ref>PMID:7608206</ref> <ref>PMID:9192629</ref> <ref>PMID:9230304</ref> <ref>PMID:9448271</ref> <ref>PMID:9790841</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Our previous paper (Wilkinson et al, 2016) used high-resolution cryo-electron microscopy to solve the structure of the Escherichia coli RecBCD complex, which acts in both the repair of double-stranded DNA breaks and the degradation of bacteriophage DNA. To counteract the latter activity, bacteriophage lambda encodes a small protein inhibitor called Gam that binds to RecBCD and inactivates the complex. Here, we show that Gam inhibits RecBCD by competing at the DNA-binding site. The interaction surface is extensive and involves molecular mimicry of the DNA substrate. We also show that expression of Gam in E. coli or Klebsiella pneumoniae increases sensitivity to fluoroquinolones; antibacterials that kill cells by inhibiting topoisomerases and inducing double-stranded DNA breaks. Furthermore, fluoroquinolone-resistance in K. pneumoniae clinical isolates is reversed by expression of Gam. Together, our data explain the synthetic lethality observed between topoisomerase-induced DNA breaks and the RecBCD gene products, suggesting a new co-antibacterial strategy. | ||
| - | + | Structural basis for the inhibition of RecBCD by Gam and its synergistic antibacterial effect with quinolones.,Wilkinson M, Troman L, Wan Nur Ismah WA, Chaban Y, Avison MB, Dillingham MS, Wigley DB Elife. 2016 Dec 23;5. pii: e22963. doi: 10.7554/eLife.22963. PMID:28009252<ref>PMID:28009252</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 5mbv" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Exodeoxyribonuclease V]] | ||
[[Category: Chaban, Y]] | [[Category: Chaban, Y]] | ||
| + | [[Category: Wigley, D B]] | ||
[[Category: Wilkinson, M]] | [[Category: Wilkinson, M]] | ||
| - | [[Category: | + | [[Category: Complex]] |
| + | [[Category: Dna binding protein]] | ||
| + | [[Category: Dna repair]] | ||
| + | [[Category: Helicase/nuclease]] | ||
| + | [[Category: Inhibitor]] | ||
Revision as of 16:34, 18 January 2017
Cryo-EM structure of Lambda Phage protein GamS bound to RecBCD
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