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3u2k

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S. aureus GyrB ATPase domain in complex with a small molecule inhibitor

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Retrieved from "http://52.214.119.220/wiki/index.php/3u2k"

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 ==S. aureus GyrB ATPase domain in complex with a small molecule inhibitor==
-<StructureSection load='3u2k' size='340' side='right' caption='[[3u2k]], [[Resolution|resolution]] 1.64&Aring;' scene=''>
+<StructureSection load='3u2k' size='340' side='right'caption='[[3u2k]], [[Resolution|resolution]] 1.64&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3u2k]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"micrococcus_aureus"_(rosenbach_1884)_zopf_1885 "micrococcus aureus" (rosenbach 1884) zopf 1885]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U2K OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U2K FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3u2k]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3U2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U2K FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=087:2-CHLORO-6-(4-{[(3,4-DICHLORO-5-METHYL-1H-PYRROL-2-YL)CARBONYL]AMINO}PIPERIDIN-1-YL)PYRIDINE-4-CARBOXAMIDE'>087</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.64&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3ttz|3ttz]], [[3u2d|3u2d]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=087:2-CHLORO-6-(4-{[(3,4-DICHLORO-5-METHYL-1H-PYRROL-2-YL)CARBONYL]AMINO}PIPERIDIN-1-YL)PYRIDINE-4-CARBOXAMIDE'>087</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gyrB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1280 "Micrococcus aureus" (Rosenbach 1884) Zopf 1885])</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=3u2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u2k OCA], [https://pdbe.org/3u2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u2k RCSB], [https://www.ebi.ac.uk/pdbsum/3u2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u2k ProSAT]</span></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_topoisomerase_(ATP-hydrolyzing) DNA topoisomerase (ATP-hydrolyzing)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.99.1.3 5.99.1.3] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3u2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u2k OCA], [http://pdbe.org/3u2k PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3u2k RCSB], [http://www.ebi.ac.uk/pdbsum/3u2k PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3u2k ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/GYRB_STAAU GYRB_STAAU]] DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.[HAMAP-Rule:MF_01898]
+[https://www.uniprot.org/uniprot/GYRB_STAAU GYRB_STAAU] DNA gyrase negatively supercoils closed circular double-stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.[HAMAP-Rule:MF_01898]
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-DNA gyrase is an essential enzyme in bacteria and its inhibition results in the disruption of DNA synthesis and subsequently cell death. The pyrrolamides are a novel class of antibacterial agents targeting DNA gyrase. These compounds were identified from a fragment-based lead generation (FBLG) approach using NMR screening to identify low molecular weight compounds that bind to the ATP pocket of DNA gyrase. A pyrrole hit with a binding constant of 1 mM formed the basis of the design and synthesis of a focused library of compounds that resulted in the rapid identification of a lead compound that inhibited DNA gyrase with an IC(50) value of 3 muM. The potency of the lead compound was further optimized utilizing iterative X-ray crystallography to yield DNA gyrase inhibitors that also displayed antibacterial activity. Spontaneous mutants were isolated in Staphylococcus aureus by plating on agar plates containing pyrrolamide 4 at the MIC. The resistant variants displayed 4- to 8-fold increased MIC values relative to the parent strain. DNA sequencing revealed two independent point mutations in the pyrrolamide binding region of the gyrB gene from these variants, supporting the hypothesis that the mode-of-action of these compounds was inhibition of DNA gyrase. Efficacy of a representative pyrrolamide was demonstrated against Streptococcus pneumoniae in a mouse lung infection model. These data demonstrate that the pyrrolamides are a novel class of DNA gyrase inhibitors with the potential to deliver future antibacterial agents targeting multiple clinical indications.
-Pyrrolamide DNA Gyrase Inhibitors: Fragment-based NMR Screening to Antibacterial Agents.,Eakin AE, Green O, Hales N, Walkup GK, Bist S, Singh A, Mullen G, Bryant J, Embrey K, Gao N, Breeze A, Timms D, Andrews B, Uria-Nickelsen M, Demeritt J, Loch JT 3rd, Hull K, Blodgett A, Illingworth RN, Prince B, Boriack-Sjodin PA, Hauck S, Macpherson LJ, Ni H, Sherer B Antimicrob Agents Chemother. 2011 Dec 19. PMID:22183167<ref>PMID:22183167</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 3u2k" style="background-color:#fffaf0;"></div>
 ==See Also==
-*[[Gyrase|Gyrase]]
+*[[Gyrase 3D Structures|Gyrase 3D Structures]]
-== References ==
-<references/>
 __TOC__
 </StructureSection>
-[[Category: Boriack-Sjodin, P A]]
+[[Category: Large Structures]]
-[[Category: Eakin, A E]]
+[[Category: Staphylococcus aureus]]
-[[Category: Prince, D B]]
+[[Category: Boriack-Sjodin PA]]
-[[Category: Sherer, B A]]
+[[Category: Eakin AE]]
-[[Category: Antimicrobial]]
+[[Category: Prince DB]]
-[[Category: Atp-binding]]
+[[Category: Sherer BA]]
-[[Category: Isomerase-isomerase inhibitor complex]]
-[[Category: Protein-inhibitor complex]]
-[[Category: Structure-based drug design]]

3u2k

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S. aureus GyrB ATPase domain in complex with a small molecule inhibitor

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