View source for 6yd9


==Ecoli GyrB24 with inhibitor 16a==
<StructureSection load='6yd9' size='340' side='right'caption='[[6yd9]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6yd9]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6YD9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6YD9 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]] 1.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=ON2:N-[6-(3-azanylpropanoylamino)-1,3-benzothiazol-2-yl]-3,4-bis(chloranyl)-5-methyl-1H-pyrrole-2-carboxamide'>ON2</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=6yd9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6yd9 OCA], [https://pdbe.org/6yd9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6yd9 RCSB], [https://www.ebi.ac.uk/pdbsum/6yd9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6yd9 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GYRB_ECOLI GYRB_ECOLI] 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.<ref>PMID:12051843</ref> <ref>PMID:18642932</ref> <ref>PMID:20675723</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We designed and synthesized a series of inhibitors of the bacterial enzymes DNA gyrase and DNA topoisomerase IV, based on our recently published benzothiazole-based inhibitor bearing an oxalyl moiety. To improve the antibacterial activity and retain potent enzymatic activity, we systematically explored the chemical space. Several strategies of modification were followed: varying substituents on the pyrrole carboxamide moiety, alteration of the central scaffold, including variation of substitution position and, most importantly, modification of the oxalyl moiety. Compounds with acidic, basic, and neutral properties were synthesized. To understand the mechanism of action and binding mode, we have obtained a crystal structure of compound 16a, bearing a primary amino group, in complex with the N-terminal domain of E. coli gyrase B (24 kDa) (PDB: 6YD9). Compound 15a, with a low molecular weight of 383 Da, potent inhibitory activity on E. coli gyrase (IC50 = 9.5 nM), potent antibacterial activity on E. faecalis (MIC = 3.13 muM), and efflux impaired E. coli strain (MIC = 0.78 muM), is an important contribution for the development of novel gyrase and topoisomerase IV inhibitors in Gram-negative bacteria.

Exploring the Chemical Space of Benzothiazole-Based DNA Gyrase B Inhibitors.,Skok Z, Barancokova M, Benek O, Cruz CD, Tammela P, Tomasic T, Zidar N, Masic LP, Zega A, Stevenson CEM, Mundy JEA, Lawson DM, Maxwell A, Kikelj D, Ilas J ACS Med Chem Lett. 2020 Oct 15;11(12):2433-2440. doi:, 10.1021/acsmedchemlett.0c00416. eCollection 2020 Dec 10. PMID:33329764<ref>PMID:33329764</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6yd9" style="background-color:#fffaf0;"></div>

==See Also==
*[[Gyrase 3D Structures|Gyrase 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Barancokova M]]
[[Category: Benek O]]
[[Category: Cruz CD]]
[[Category: Ilas J]]
[[Category: Kikelj D]]
[[Category: Lawson DM]]
[[Category: Masic LP]]
[[Category: Maxwell AM]]
[[Category: Mundy J]]
[[Category: Skok Z]]
[[Category: Stevenson CEM]]
[[Category: Tammela P]]
[[Category: Tomasic T]]
[[Category: Zega A]]
[[Category: Zidar N]]