View source for 4zvi


==GYRASE B IN COMPLEX WITH 4,5-DIBROMOPYRROLAMIDE-BASED INHIBITOR==
<StructureSection load='4zvi' size='340' side='right'caption='[[4zvi]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4zvi]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4ZVI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4ZVI 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]] 2.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4S4:N-(4-{[(4,5-DIBROMO-1H-PYRROL-2-YL)CARBONYL]AMINO}BENZOYL)GLYCINE'>4S4</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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=4zvi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4zvi OCA], [https://pdbe.org/4zvi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4zvi RCSB], [https://www.ebi.ac.uk/pdbsum/4zvi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4zvi ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GYRB_ECO57 GYRB_ECO57] 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 ==
Bacterial DNA gyrase is a well-known and validated target in the design of antibacterial drugs. However, inhibitors of its ATP binding subunit, DNA gyrase B (GyrB), have so far not reached clinical use. In the present study, three different series of N-phenyl-4,5-dibromopyrrolamides and N-phenylindolamides were designed and prepared as potential DNA gyrase B inhibitors. The IC50 values of compounds on DNA gyrase from Escherichia coli were in the low micromolar range, with the best compound, (4-(4,5-dibromo-1H-pyrrole-2-carboxamido)benzoyl)glycine (6a), displaying an IC50 of 450 nM. For this compound a high-resolution crystal structure in complex with E. coli DNA gyrase B was obtained, revealing details of its binding mode within the active site. The binding affinities of three compounds with GyrB were additionally evaluated by surface plasmon resonance and the results were in good agreement with the determined enzymatic activities. For the most promising compounds the inhibitory activities against DNA gyrase from Staphylococcus aureus and topoisomerases IV from E. coli and S. aureus were determined. Antibacterial activities of the most potent compounds of each series were evaluated against two Gram-positive and two Gram-negative bacterial strains. The results obtained in this study provide valuable information on the binding mode and structure-activity relationship of N-phenyl-4,5-dibromopyrrolamides and N-phenylindolamides as promising classes of ATP competitive GyrB inhibitors.

N-Phenyl-4,5-dibromopyrrolamides and N-Phenylindolamides as ATP competitive DNA Gyrase B Inhibitors: Design, Synthesis, and Evaluation.,Zidar N, Macut H, Tomasic T, Brvar M, Montalvao S, Tammela P, Solmajer TJ, Peretlin Masic L, Ilas J, Kikelj D J Med Chem. 2015 Jun 30. PMID:26126187<ref>PMID:26126187</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4zvi" style="background-color:#fffaf0;"></div>

==See Also==
*[[Gyrase 3D Structures|Gyrase 3D Structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Large Structures]]
[[Category: Brvar M]]
[[Category: Ilas J]]
[[Category: Kikelj D]]
[[Category: Macut H]]
[[Category: Montalvao S]]
[[Category: Peterlin Masic L]]
[[Category: Solmajer T]]
[[Category: Tammela P]]
[[Category: Tomasic T]]
[[Category: Zidar N]]