5l3j: Difference between revisions

Latest revision as of 16:05, 4 October 2023

ESCHERICHIA COLI DNA GYRASE B IN COMPLEX WITH BENZOTHIAZOLE-BASED INHIBITOR

Structural highlights

5l3j 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 2.83Å
Ligands:	6G9, IOD
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

Bacterial DNA gyrase and topoisomerase IV control the topological state of DNA during replication and are validated targets for antibacterial drug discovery. Starting from our recently reported 4,5,6,7-tetrahydrobenzo[1,2-d]thiazole-based DNA gyrase B inhibitors, we replaced their central core with benzothiazole-2,6-diamine scaffold and interchanged substituents in positions 2 and 6. This resulted in equipotent nanomolar inhibitors of DNA gyrase from Escherichia coli displaying improved inhibition of Staphylococcus aureus DNA gyrase and topoisomerase IV from both bacteria. Compound 27 was the most balanced inhibitor of DNA gyrase and topoisomerase IV both from E. coli and S. aureus. The crystal structure of the 2-((2-(4,5-dibromo-1H-pyrrole-2-carboxamido)benzothiazol-6-yl)amino)-2-oxoacetic acid (24) in complex with E. coli DNA gyrase B revealed the binding mode of the inhibitor in the ATP-binding pocket. Only some compounds possessed weak antibacterial activity against Gram-positive bacteria. These results provide a basis for structure-based optimization towards dual DNA gyrase and topoisomerase IV inhibitors with antibacterial activity.

Discovery of Benzothiazole Scaffold-Based DNA Gyrase B Inhibitors.,Gjorgjieva M, Tomasic T, Barancokova M, Katsamakas S, Ilas J, Tammela P, Peterlin Masic L, Kikelj D J Med Chem. 2016 Aug 19. PMID:27541007^[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
↑ Gjorgjieva M, Tomasic T, Barancokova M, Katsamakas S, Ilas J, Tammela P, Peterlin Masic L, Kikelj D. Discovery of Benzothiazole Scaffold-Based DNA Gyrase B Inhibitors. J Med Chem. 2016 Aug 19. PMID:27541007 doi:https://dx.doi.org/10.1021/acs.jmedchem.6b00864

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] Gjorgjieva M, Tomasic T, Barancokova M, Katsamakas S, Ilas J, Tammela P, Peterlin Masic L, Kikelj D. Discovery of Benzothiazole Scaffold-Based DNA Gyrase B Inhibitors. J Med Chem. 2016 Aug 19. PMID:27541007 doi:https://dx.doi.org/10.1021/acs.jmedchem.6b00864

[1]

[2]

[3]

[4]

@@ Line 3: / Line 3: @@
 <StructureSection load='5l3j' size='340' side='right'caption='[[5l3j]], [[Resolution|resolution]] 2.83&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5l3j]] 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=5L3J OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5L3J FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5l3j]] 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=5L3J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5L3J FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6G9:2-[[2-[[4,5-BIS(BROMANYL)-1~{H}-PYRROL-2-YL]CARBONYLAMINO]-1,3-BENZOTHIAZOL-6-YL]AMINO]-2-OXIDANYLIDENE-ETHANOIC+ACID'>6G9</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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]] 2.83&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gyrB, Z5190, ECs4634 ([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=6G9:2-[[2-[[4,5-BIS(BROMANYL)-1~{H}-PYRROL-2-YL]CARBONYLAMINO]-1,3-BENZOTHIAZOL-6-YL]AMINO]-2-OXIDANYLIDENE-ETHANOIC+ACID'>6G9</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</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_(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'>[https://proteopedia.org/fgij/fg.htm?mol=5l3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l3j OCA], [https://pdbe.org/5l3j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5l3j RCSB], [https://www.ebi.ac.uk/pdbsum/5l3j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5l3j 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=5l3j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5l3j OCA], [http://pdbe.org/5l3j PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5l3j RCSB], [http://www.ebi.ac.uk/pdbsum/5l3j PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5l3j ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://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>
+[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 27: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Bacillus coli migula 1895]]
+[[Category: Escherichia coli]]
 [[Category: Large Structures]]
-[[Category: Barancokova, M]]
+[[Category: Barancokova M]]
-[[Category: Gjorgjieva, M]]
+[[Category: Gjorgjieva M]]
-[[Category: Ilas, J]]
+[[Category: Ilas J]]
-[[Category: Katsamakas, S]]
+[[Category: Katsamakas S]]
-[[Category: Kikelj, D]]
+[[Category: Kikelj D]]
-[[Category: Masic, L Peterlin]]
+[[Category: Montalvao S]]
-[[Category: Montalvao, S]]
+[[Category: Peterlin Masic L]]
-[[Category: Tammella, P]]
+[[Category: Tammella P]]
-[[Category: Tomasic, T]]
+[[Category: Tomasic T]]
-[[Category: Complex]]
-[[Category: Gyrase b]]
-[[Category: Gyrb]]
-[[Category: Inhibitor]]
-[[Category: Isomerase]]
-[[Category: Proteros biostructure]]
-[[Category: Proteros biostructures gmbh]]

5l3j: Difference between revisions

Latest revision as of 16:05, 4 October 2023

ESCHERICHIA COLI DNA GYRASE B IN COMPLEX WITH BENZOTHIAZOLE-BASED INHIBITOR

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools