7c7n: Difference between revisions

Latest revision as of 15:58, 29 November 2023

Crystal structure of E.coli DNA gyrase B in complex with 6-fluoro-8-(methylamino)-2-oxo-1,2-dihydroquinoline derivative

Structural highlights

7c7n is a 1 chain structure with sequence from Escherichia coli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.3Å
Ligands:	FKR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Noble CG, Maxwell A. The role of GyrB in the DNA cleavage-religation reaction of DNA gyrase: a proposed two metal-ion mechanism. J Mol Biol. 2002 Apr 26;318(2):361-71. PMID:12051843 doi:https://dx.doi.org/10.1016/S0022-2836(02)00049-9
↑ Sissi C, Chemello A, Vazquez E, Mitchenall LA, Maxwell A, Palumbo M. DNA gyrase requires DNA for effective two-site coordination of divalent metal ions: further insight into the mechanism of enzyme action. Biochemistry. 2008 Aug 19;47(33):8538-45. doi: 10.1021/bi800480j. Epub 2008 Jul, 22. PMID:18642932 doi:https://dx.doi.org/10.1021/bi800480j
↑ Schoeffler AJ, May AP, Berger JM. A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a critical role in gyrase function. Nucleic Acids Res. 2010 Jul 31. PMID:20675723 doi:10.1093/nar/gkq665
↑ 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. Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors. Bioorg Med Chem. 2020 Sep 22;28(22):115776. doi: 10.1016/j.bmc.2020.115776. PMID:33032189 doi:https://dx.doi.org/10.1016/j.bmc.2020.115776

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Noble CG, Maxwell A. The role of GyrB in the DNA cleavage-religation reaction of DNA gyrase: a proposed two metal-ion mechanism. J Mol Biol. 2002 Apr 26;318(2):361-71. PMID:12051843 doi:https://dx.doi.org/10.1016/S0022-2836(02)00049-9

[2] Sissi C, Chemello A, Vazquez E, Mitchenall LA, Maxwell A, Palumbo M. DNA gyrase requires DNA for effective two-site coordination of divalent metal ions: further insight into the mechanism of enzyme action. Biochemistry. 2008 Aug 19;47(33):8538-45. doi: 10.1021/bi800480j. Epub 2008 Jul, 22. PMID:18642932 doi:https://dx.doi.org/10.1021/bi800480j

[3] Schoeffler AJ, May AP, Berger JM. A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a critical role in gyrase function. Nucleic Acids Res. 2010 Jul 31. PMID:20675723 doi:10.1093/nar/gkq665

[4] 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. Lead optimization of 8-(methylamino)-2-oxo-1,2-dihydroquinolines as bacterial type II topoisomerase inhibitors. Bioorg Med Chem. 2020 Sep 22;28(22):115776. doi: 10.1016/j.bmc.2020.115776. PMID:33032189 doi:https://dx.doi.org/10.1016/j.bmc.2020.115776

[1]

[2]

[3]

[4]

@@ Line 3: / Line 3: @@
 <StructureSection load='7c7n' size='340' side='right'caption='[[7c7n]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7c7n]] is a 1 chain structure with sequence from [http://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=7C7N OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7C7N FirstGlance]. <br>
+<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='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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gyrB, NCTC10766_01911, NCTC9007_05029 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_topoisomerase DNA topoisomerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.6.2.2 5.6.2.2] </span></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>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7c7n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7c7n OCA], [http://pdbe.org/7c7n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7c7n RCSB], [http://www.ebi.ac.uk/pdbsum/7c7n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7c7n ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/A0A210GCC1_ECOLX A0A210GCC1_ECOLX]] A type II topoisomerase that negatively supercoils closed circular double-stranded (ds) DNA in an ATP-dependent manner to modulate DNA topology and maintain chromosomes in an underwound state. Negative supercoiling favors strand separation, and DNA replication, transcription, recombination and repair, all of which involve strand separation. Also able to catalyze the interconversion of other topological isomers of dsDNA rings, including catenanes and knotted rings. Type II topoisomerases break and join 2 DNA strands simultaneously in an ATP-dependent manner.[HAMAP-Rule:MF_01898]
+[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 ==
@@ Line 20: / Line 19: @@
 </div>
 <div class="pdbe-citations 7c7n" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Gyrase 3D Structures|Gyrase 3D Structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Bacillus coli migula 1895]]
+[[Category: Escherichia coli]]
-[[Category: DNA topoisomerase]]
 [[Category: Large Structures]]
-[[Category: Mima, M]]
+[[Category: Mima M]]
-[[Category: Ushiyama, F]]
+[[Category: Ushiyama F]]
-[[Category: Complex]]
-[[Category: Escherichia coli]]
-[[Category: Inhibitor]]
-[[Category: Isomerase]]
-[[Category: Topoisomerase]]

7c7n: Difference between revisions

Latest revision as of 15:58, 29 November 2023

Crystal structure of E.coli DNA gyrase B in complex with 6-fluoro-8-(methylamino)-2-oxo-1,2-dihydroquinoline derivative

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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