View source for 2q7u


==Crystal Structure of the F plasmid TraI Relaxase Domain with the Scissile Thymidine Base and Imidodiphosphate==
<StructureSection load='2q7u' size='340' side='right'caption='[[2q7u]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2q7u]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Q7U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q7U FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=PON:IMIDO+DIPHOSPHATE'>PON</scene>, <scene name='pdbligand=TMP:THYMIDINE-5-PHOSPHATE'>TMP</scene></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=2q7u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q7u OCA], [https://pdbe.org/2q7u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q7u RCSB], [https://www.ebi.ac.uk/pdbsum/2q7u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q7u ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TRAI1_ECOLI TRAI1_ECOLI] Conjugative DNA transfer (CDT) is the unidirectional transfer of ssDNA plasmid from a donor to a recipient cell. It is the central mechanism by which antibiotic resistance and virulence factors are propagated in bacterial populations. Part of the relaxosome, which facilitates a site- and strand-specific cut in the origin of transfer by TraI, at the nic site. Relaxosome formation requires binding of IHF and TraY to the oriT region, which then faciliates binding of TraI relaxase. TraI forms a covalent 5'-phosphotyrosine intermediate linkage to the ssDNA. The transesterified T-strand moves from the donor cell to the recipient cell in a 5'to 3' direction, with the DNA helicase activity of TraI unwinding the DNA. DNA transfer occurs via the conjugative pore (transferosome) an intercellular junction mediated by a type IV secretion system, with TraD providing the means to link the relaxosome to the conjugative pore. The relaxase completes DNA transfer by reversing the covalent phosphotyrosine linkage and releasing the T-strand.<ref>PMID:12637015</ref> <ref>PMID:6308637</ref> <ref>PMID:8386720</ref> <ref>PMID:7499339</ref> <ref>PMID:11560509</ref>   TraI has also been identified as DNA helicase I. DNA. helicase I is a potent, highly processive DNA-dependent ATPase, able to unwind about 1.1 kb dsDNA per second in a 5' to 3' manner.<ref>PMID:12637015</ref> <ref>PMID:6308637</ref> <ref>PMID:8386720</ref> <ref>PMID:7499339</ref> <ref>PMID:11560509</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/q7/2q7u_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2q7u ConSurf].
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== Publication Abstract from PubMed ==
Conjugative transfer of plasmid DNA via close cell-cell junctions is the main route by which antibiotic resistance genes spread between bacterial strains. Relaxases are essential for conjugative transfer and act by cleaving DNA strands and forming covalent phosphotyrosine linkages. Based on data indicating that multityrosine relaxase enzymes can accommodate two phosphotyrosine intermediates within their divalent metal-containing active sites, we hypothesized that bisphosphonates would inhibit relaxase activity and conjugative DNA transfer. We identified bisphosphonates that are nanomolar inhibitors of the F plasmid conjugative relaxase in vitro. Furthermore, we used cell-based assays to demonstrate that these compounds are highly effective at preventing DNA transfer and at selectively killing cells harboring conjugative plasmids. Two potent inhibitors, clodronate and etidronate, are already clinically approved to treat bone loss. Thus, the inhibition of conjugative relaxases is a potentially novel antimicrobial approach, one that selectively targets bacteria capable of transferring antibiotic resistance and generating multidrug resistant strains.

Disrupting antibiotic resistance propagation by inhibiting the conjugative DNA relaxase.,Lujan SA, Guogas LM, Ragonese H, Matson SW, Redinbo MR Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12282-7. Epub 2007 Jul 13. PMID:17630285<ref>PMID:17630285</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2q7u" style="background-color:#fffaf0;"></div>

==See Also==
*[[Helicase 3D structures|Helicase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Lujan SA]]
[[Category: Redinbo MR]]