View source for 5mbv


==Cryo-EM structure of Lambda Phage protein GamS bound to RecBCD.==
<SX load='5mbv' size='340' side='right' viewer='molstar' caption='[[5mbv]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5mbv]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Escherichia_virus_Lambda Escherichia virus Lambda]. 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 [https://proteopedia.org/fgij/fg.htm?mol=5MBV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.8&#8491;</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=5mbv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mbv OCA], [https://pdbe.org/5mbv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mbv RCSB], [https://www.ebi.ac.uk/pdbsum/5mbv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mbv ProSAT]</span></td></tr>
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== Function ==
[https://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> 
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== 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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Exonuclease 3D structures|Exonuclease 3D structures]]
== References ==
<references/>
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[[Category: Escherichia coli]]
[[Category: Escherichia virus Lambda]]
[[Category: Large Structures]]
[[Category: Chaban Y]]
[[Category: Wigley DB]]
[[Category: Wilkinson M]]