7c7n: Difference between revisions
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==Crystal structure of E.coli DNA gyrase B in complex with 6-fluoro-8-(methylamino)-2-oxo-1,2-dihydroquinoline derivative== | |||
<StructureSection load='7c7n' size='340' side='right'caption='[[7c7n]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7c7n]] 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=7C7N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7C7N 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]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FKR:4-[[6-fluoranyl-8-(methylamino)-2-oxidanylidene-1~{H}-quinolin-3-yl]carbonylamino]benzoic+acid'>FKR</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=7c7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c7n OCA], [https://pdbe.org/7c7n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7c7n RCSB], [https://www.ebi.ac.uk/pdbsum/7c7n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7c7n 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 == | |||
The global increase in multidrug-resistant pathogens has caused severe problems in the treatment of infections. To overcome these difficulties, the advent of a new chemical class of antibacterial drug is eagerly desired. We aimed at creating novel antibacterial agents against bacterial type II topoisomerases, which are well-validated targets. TP0480066 (compound 32) has been identified by using structure-based optimization originated from lead compound 1, which was obtained as a result of our previous lead identification studies. The MIC90 values of TP0480066 against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and genotype penicillin-resistant Streptococcus pneumoniae (gPRSP) were 0.25, 0.015, and 0.06 mug/mL, respectively. Hence, TP0480066 can be regarded as a promising antibacterial drug candidate of this chemical class. | |||
Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors.,Ushiyama F, Amada H, Mihara Y, Takeuchi T, Tanaka-Yamamoto N, Mima M, Kamitani M, Wada R, Tamura Y, Endo M, Masuko A, Takata I, Hitaka K, Sugiyama H, Ohtake N Bioorg Med Chem. 2020 Sep 22;28(22):115776. doi: 10.1016/j.bmc.2020.115776. PMID:33032189<ref>PMID:33032189</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Mima | <div class="pdbe-citations 7c7n" style="background-color:#fffaf0;"></div> | ||
[[Category: Ushiyama | |||
==See Also== | |||
*[[Gyrase 3D Structures|Gyrase 3D Structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Escherichia coli]] | |||
[[Category: Large Structures]] | |||
[[Category: Mima M]] | |||
[[Category: Ushiyama F]] | |||
Latest revision as of 18:58, 29 November 2023
Crystal structure of E.coli DNA gyrase B in complex with 6-fluoro-8-(methylamino)-2-oxo-1,2-dihydroquinoline derivativeCrystal structure of E.coli DNA gyrase B in complex with 6-fluoro-8-(methylamino)-2-oxo-1,2-dihydroquinoline derivative
Structural highlights
FunctionGYRB_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.[1] [2] [3] Publication Abstract from PubMedThe global increase in multidrug-resistant pathogens has caused severe problems in the treatment of infections. To overcome these difficulties, the advent of a new chemical class of antibacterial drug is eagerly desired. We aimed at creating novel antibacterial agents against bacterial type II topoisomerases, which are well-validated targets. TP0480066 (compound 32) has been identified by using structure-based optimization originated from lead compound 1, which was obtained as a result of our previous lead identification studies. The MIC90 values of TP0480066 against methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococci (VRE), and genotype penicillin-resistant Streptococcus pneumoniae (gPRSP) were 0.25, 0.015, and 0.06 mug/mL, respectively. Hence, TP0480066 can be regarded as a promising antibacterial drug candidate of this chemical class. Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors.,Ushiyama F, Amada H, Mihara Y, Takeuchi T, Tanaka-Yamamoto N, Mima M, Kamitani M, Wada R, Tamura Y, Endo M, Masuko A, Takata I, Hitaka K, Sugiyama H, Ohtake N Bioorg Med Chem. 2020 Sep 22;28(22):115776. doi: 10.1016/j.bmc.2020.115776. PMID:33032189[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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