3b6c

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[[Image:3b6c.jpg|left|200px]]<br /><applet load="3b6c" size="350" color="white" frame="true" align="right" spinBox="true"
 
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caption="3b6c, resolution 2.30&Aring;" />
 
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'''Crystal structure of the Streptomyces coelicolor TetR family protein ActR in complex with (S)-DNPA'''<br />
 
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==Overview==
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==Crystal structure of the Streptomyces coelicolor TetR family protein ActR in complex with (S)-DNPA==
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Actinorhodin, an antibiotic produced by Streptomyces coelicolor, is, exported from the cell by the ActA efflux pump. actA is divergently, transcribed from actR, which encodes a TetR-like transcriptional, repressor. We showed previously that ActR represses transcription by, binding to an operator from the actA/actR intergenic region. Importantly, actinorhodin itself or various actinorhodin biosynthetic intermediates can, cause ActR to dissociate from its operator, leading to derepression. This, suggests that ActR may mediate timely self-resistance to an endogenously, produced antibiotic by responding to one of its biosynthetic precursors., Here, we report the structural basis for this precursor-mediated, derepression with crystal structures of homodimeric ActR by itself and in, complex with either actinorhodin or the actinorhodin biosynthetic, intermediate (S)-DNPA, [4-dihydro-9-hydroxy-1-methyl-10-oxo-3-H-naphtho-[2,3-c]-pyran-3-(S)-aceti, c acid]. The ligand-binding tunnel in each ActR monomer has a striking, hydrophilic/hydrophobic/hydrophilic arrangement of surface residues that, accommodate either one hexacyclic actinorhodin molecule or two, back-to-back tricyclic (S)-DNPA molecules. Moreover, our work also reveals, the strongest structural evidence to date that TetR-mediated antibiotic, resistance may have been acquired from an antibiotic-producer organism.
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<StructureSection load='3b6c' size='340' side='right'caption='[[3b6c]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3b6c]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptomyces_coelicolor Streptomyces coelicolor]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B6C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3B6C FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SDN:[(3S)-9-HYDROXY-1-METHYL-10-OXO-4,10-DIHYDRO-3H-BENZO[G]ISOCHROMEN-3-YL]ACETIC+ACID'>SDN</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3b6c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3b6c OCA], [https://pdbe.org/3b6c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3b6c RCSB], [https://www.ebi.ac.uk/pdbsum/3b6c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3b6c ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/Q53901_STRCH Q53901_STRCH]
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/b6/3b6c_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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=3b6c ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Actinorhodin, an antibiotic produced by Streptomyces coelicolor, is exported from the cell by the ActA efflux pump. actA is divergently transcribed from actR, which encodes a TetR-like transcriptional repressor. We showed previously that ActR represses transcription by binding to an operator from the actA/actR intergenic region. Importantly, actinorhodin itself or various actinorhodin biosynthetic intermediates can cause ActR to dissociate from its operator, leading to derepression. This suggests that ActR may mediate timely self-resistance to an endogenously produced antibiotic by responding to one of its biosynthetic precursors. Here, we report the structural basis for this precursor-mediated derepression with crystal structures of homodimeric ActR by itself and in complex with either actinorhodin or the actinorhodin biosynthetic intermediate (S)-DNPA [4-dihydro-9-hydroxy-1-methyl-10-oxo-3-H-naphtho-[2,3-c]-pyran-3-(S)-aceti c acid]. The ligand-binding tunnel in each ActR monomer has a striking hydrophilic/hydrophobic/hydrophilic arrangement of surface residues that accommodate either one hexacyclic actinorhodin molecule or two back-to-back tricyclic (S)-DNPA molecules. Moreover, our work also reveals the strongest structural evidence to date that TetR-mediated antibiotic resistance may have been acquired from an antibiotic-producer organism.
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==About this Structure==
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Crystal structures of the Streptomyces coelicolor TetR-like protein ActR alone and in complex with actinorhodin or the actinorhodin biosynthetic precursor (S)-DNPA.,Willems AR, Tahlan K, Taguchi T, Zhang K, Lee ZZ, Ichinose K, Junop MS, Nodwell JR J Mol Biol. 2008 Mar 7;376(5):1377-87. Epub 2008 Jan 4. PMID:18207163<ref>PMID:18207163</ref>
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3B6C is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_coelicolor Streptomyces coelicolor] with <scene name='pdbligand=SDN:'>SDN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Known structural/functional Sites: <scene name='pdbsite=AC1:Sdn+Binding+Site+For+Residue+A+301'>AC1</scene>, <scene name='pdbsite=AC2:Sdn+Binding+Site+For+Residue+A+302'>AC2</scene> and <scene name='pdbsite=AC3:Sdn+Binding+Site+For+Residue+B+303'>AC3</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3B6C OCA].
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==Reference==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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Crystal Structures of the Streptomyces coelicolor TetR-Like Protein ActR Alone and in Complex with Actinorhodin or the Actinorhodin Biosynthetic Precursor (S)-DNPA., Willems AR, Tahlan K, Taguchi T, Zhang K, Lee ZZ, Ichinose K, Junop MS, Nodwell JR, J Mol Biol. 2008 Jan 4;. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=18207163 18207163]
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</div>
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[[Category: Single protein]]
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<div class="pdbe-citations 3b6c" style="background-color:#fffaf0;"></div>
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[[Category: Streptomyces coelicolor]]
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[[Category: Junop, M.S.]]
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[[Category: Willems, A.R.]]
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[[Category: SDN]]
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[[Category: (s)-dnpa]]
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[[Category: actinorhodin]]
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[[Category: dna-binding protein]]
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[[Category: ligand]]
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[[Category: tetr family]]
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[[Category: transcription regulation]]
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[[Category: transcriptional repressor]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 13 08:15:16 2008''
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==See Also==
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*[[Tetracycline repressor protein 3D structures|Tetracycline repressor protein 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Streptomyces coelicolor]]
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[[Category: Junop MS]]
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[[Category: Willems AR]]

Current revision

Crystal structure of the Streptomyces coelicolor TetR family protein ActR in complex with (S)-DNPA

PDB ID 3b6c

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