6u18

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==Directed evolution of a biosensor selective for the macrolide antibiotic clarithromycin==
==Directed evolution of a biosensor selective for the macrolide antibiotic clarithromycin==
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<StructureSection load='6u18' size='340' side='right'caption='[[6u18]]' scene=''>
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<StructureSection load='6u18' size='340' side='right'caption='[[6u18]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U18 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6U18 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6u18]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6U18 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U18 FirstGlance]. <br>
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</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6u18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u18 OCA], [http://pdbe.org/6u18 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u18 RCSB], [http://www.ebi.ac.uk/pdbsum/6u18 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u18 ProSAT]</span></td></tr>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CTY:CLARITHROMYCIN'>CTY</scene>, <scene name='pdbligand=FLC:CITRATE+ANION'>FLC</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mphR(A), mphR, A9R57_28010, ACN77_02555, ACN77_03810, ACN77_19745, AKG29_00740, AM465_27045, APT94_14580, B1K96_22845, B9M99_28120, B9N33_26285, B9T59_28650, BANRA_01808, BANRA_05330, BANRA_05395, BE963_00530, BEN53_26070, BET08_23460, BFD68_26430, BJJ90_27670, BK248_28255, BK292_28800, BK334_26705, BK373_25645, BK375_28450, BK383_16415, BK400_25090, BVL39_07785, BVL39_26565, C5N07_27930, C5P01_27745, C5P43_14800, C5P44_28315, C6669_28285, C6986_31345, C7235_25300, C7235_26770, CQP61_00550, CR538_26710, CRT43_27530, CRT46_27035, CWS33_26295, D0X26_00055, D0X26_28400, D3O91_28140, D9N32_01235, DB359_27590, DBY14_07355, DBY14_07475, DBY14_07595, DBY14_07715, DBY14_07835, DBY14_07955, DBY14_08075, DBY14_08195, DBY14_08400, DBY14_09000, DBY14_09120, DBY14_09240, DBY14_09360, DBY14_09480, DBY14_09600, DBY14_09720, DBY14_09840, DBY14_09960, DBY14_10080, DBY14_10200, DBY14_10320, DBY14_10440, DBY14_10560, DBY14_10680, DBY14_10800, DBY14_10920, DBY14_11040, DBY14_11160, DBY14_11280, DL545_01125, DL545_26270, DM102_26995, DM129_26600, DM129_28140, DNQ41_27340, DS732_30515, E4Z89_24290, Eco118UI_26585, ECONIH1_26780, ECTO124_05297, EGT48_01470, EIA21_26670, EJC48_00900, EJC75_00560, EJH97_25820, EPS71_24560, EQ823_24865, EQ830_27025, ERS085366_04056, ERS085404_05054, ERS150873_04751, ETN48_p0081, EVY21_24885, ExPECSC022_02556, ExPECSC036_03428, ExPECSC065_05093, EXX13_27025, EYD11_23970, FORC82_p029, HmCmsJML146_04799, HMPREF3040_01640, MS6198_B124, MS8345_A00020, NCTC13846_04922, U12A_A00163, U14A_A00115, UN86_19865, YDC107_4984 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=6u18 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u18 OCA], [https://pdbe.org/6u18 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u18 RCSB], [https://www.ebi.ac.uk/pdbsum/6u18 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u18 ProSAT]</span></td></tr>
</table>
</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Clarithromycin is an improved semisynthetic analogue of the naturally occurring macrolide, erythromycin. The subtle modification of a methyl group on the C-6 hydroxyl group endows the molecule with improved acid stability and results in a clinically useful antibiotic. Here, we show that the effector specificity of the biosensor protein, MphR, can be evolved to selectively recognize clarithromycin and therefore report on the production of this molecule in vivo. In addition, a crystal structure of the evolved variant reveals the molecular basis for selectivity and provides a guide for the evolution of a new metabolic function using this biosensor.
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Development of Genetically Encoded Biosensors for Reporting the Methyltransferase-Dependent Biosynthesis of Semisynthetic Macrolide Antibiotics.,Li Y, Reed M, Wright HT, Cropp TA, Williams GJ ACS Synth Biol. 2021 Sep 21. doi: 10.1021/acssynbio.1c00151. PMID:34546703<ref>PMID:34546703</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 6u18" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Bacillus coli migula 1895]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Cropp TA]]
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[[Category: Cropp, T A]]
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[[Category: Li Y]]
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[[Category: Li, Y]]
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[[Category: Reed M]]
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[[Category: Reed, M]]
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[[Category: Williams G]]
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[[Category: Williams, G]]
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[[Category: Wright HT]]
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[[Category: Wright, H T]]
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[[Category: Biosensor]]
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[[Category: Dna binding protein-antibiotic complex]]
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[[Category: Dna-binding]]
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[[Category: Macrolide]]

Revision as of 12:44, 13 October 2021

Directed evolution of a biosensor selective for the macrolide antibiotic clarithromycin

PDB ID 6u18

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