2f41

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(New page: 200px<br /><applet load="2f41" size="450" color="white" frame="true" align="right" spinBox="true" caption="2f41, resolution 2.50&Aring;" /> '''Crystal structure of...)
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[[Image:2f41.jpg|left|200px]]<br /><applet load="2f41" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="2f41, resolution 2.50&Aring;" />
 
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'''Crystal structure of FapR- a global regulator of fatty acid biosynthesis in B. subtilis'''<br />
 
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==Overview==
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==Crystal structure of FapR- a global regulator of fatty acid biosynthesis in B. subtilis==
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Malonyl-CoA is an essential intermediate in fatty acid synthesis in all, living cells. Here we demonstrate a new role for this molecule as a global, regulator of lipid homeostasis in Gram-positive bacteria. Using in vitro, transcription and binding studies, we demonstrate that malonyl-CoA is a, direct and specific inducer of Bacillus subtilis FapR, a conserved, transcriptional repressor that regulates the expression of several genes, involved in bacterial fatty acid and phospholipid synthesis. The crystal, structure of the effector-binding domain of FapR reveals a homodimeric, protein with a thioesterase-like 'hot-dog' fold. Binding of malonyl-CoA, promotes a disorder-to-order transition, which transforms an open, ligand-binding groove into a long tunnel occupied by the effector molecule, in the complex. This ligand-induced modification propagates to the, helix-turn-helix motifs, impairing their productive association for DNA, binding. Structure-based mutations that disrupt the FapR-malonyl-CoA, interaction prevent DNA-binding regulation and result in a lethal, phenotype in B. subtilis, suggesting this homeostatic signaling pathway as, a promising target for novel chemotherapeutic agents against Gram-positive, pathogens.
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<StructureSection load='2f41' size='340' side='right'caption='[[2f41]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
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== Structural highlights ==
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==About this Structure==
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<table><tr><td colspan='2'>[[2f41]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2F41 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2F41 FirstGlance]. <br>
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2F41 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacillus_subtilis Bacillus subtilis]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2F41 OCA].
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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]] 2.5&#8491;</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=2f41 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2f41 OCA], [https://pdbe.org/2f41 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2f41 RCSB], [https://www.ebi.ac.uk/pdbsum/2f41 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2f41 ProSAT]</span></td></tr>
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==Reference==
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</table>
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Structural basis of lipid biosynthesis regulation in Gram-positive bacteria., Schujman GE, Guerin M, Buschiazzo A, Schaeffer F, Llarrull LI, Reh G, Vila AJ, Alzari PM, de Mendoza D, EMBO J. 2006 Sep 6;25(17):4074-83. Epub 2006 Aug 24. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=16932747 16932747]
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== Function ==
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[https://www.uniprot.org/uniprot/FAPR_BACSU FAPR_BACSU] Transcription factor involved in regulation of membrane lipid biosynthesis by repressing genes involved in fatty acid and phospholipid metabolism. Binds to the 5'-TTAGTANNNNNTANTAA-3' consensus sequence found in the promoter of fabHAF operon (containing fabHA and fabF genes), yhdO and fapR genes and prevents their expression. Its action is probably modulated by malonyl-CoA.<ref>PMID:12737802</ref>
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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/f4/2f41_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=2f41 ConSurf].
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<div style="clear:both"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Bacillus subtilis]]
[[Category: Bacillus subtilis]]
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[[Category: Single protein]]
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[[Category: Large Structures]]
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[[Category: Alzari, P.M.]]
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[[Category: Alzari PM]]
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[[Category: Buschiazzo, A.]]
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[[Category: Buschiazzo A]]
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[[Category: Guerin, M.E.]]
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[[Category: Guerin ME]]
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[[Category: 'hot-dog' fold]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Wed Nov 21 10:21:10 2007''
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Current revision

Crystal structure of FapR- a global regulator of fatty acid biosynthesis in B. subtilis

PDB ID 2f41

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