6fm4
From Proteopedia
(Difference between revisions)
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<StructureSection load='6fm4' size='340' side='right'caption='[[6fm4]], [[Resolution|resolution]] 2.70Å' scene=''> | <StructureSection load='6fm4' size='340' side='right'caption='[[6fm4]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6fm4]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FM4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FM4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6fm4]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Staan Staan]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6FM4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6FM4 FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5UA:5-O-CARBOXY-2-DEOXYADENOSINE'>5UA</scene>, <scene name='pdbligand=DU5:~{N}-[3-(4-isoquinolin-1-ylpiperazin-1-yl)propyl]benzamide'>DU5</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5UA:5-O-CARBOXY-2-DEOXYADENOSINE'>5UA</scene>, <scene name='pdbligand=DU5:~{N}-[3-(4-isoquinolin-1-ylpiperazin-1-yl)propyl]benzamide'>DU5</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">gyrA, SA0006 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=158879 STAAN])</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='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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fm4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fm4 OCA], [http://pdbe.org/6fm4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fm4 RCSB], [http://www.ebi.ac.uk/pdbsum/6fm4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fm4 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6fm4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6fm4 OCA], [http://pdbe.org/6fm4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6fm4 RCSB], [http://www.ebi.ac.uk/pdbsum/6fm4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6fm4 ProSAT]</span></td></tr> | ||
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/GYRB_STAAN GYRB_STAAN]] 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 (By similarity). | [[http://www.uniprot.org/uniprot/GYRB_STAAN GYRB_STAAN]] 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 (By similarity). | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Bacterial resistance is increasing rapidly, requiring urgent identification of new antibacterial drugs that are effective against multidrug-resistant pathogens. Novel bacterial topoisomerase inhibitors (NBTIs) provide a new strategy for investigating the well validated DNA gyrase and topoisomerase IV targets, while preventing cross resistance issues. On this basis, starting from a virtual screening campaign and subsequent structure-based hit optimization guided by X-ray studies, a novel class of piperazine-like NBTIs with outstanding enzymatic activity against Staphylococcus aureus and Escherichia coli DNA gyrase and topoisomerase IV was identified. Notably, compounds (+/-)-33, (+/-)-35, and (+/-)-36 with potent and balance multitarget enzymatic profiles, exhibited excellent efficacy against selected Gram-positive and Gram-negative pathogens, as well as clinically relevant resistant strains. Overall, the new NBTI chemotype described herein, thanks to the broad-spectrum antibacterial activity and the favourable in vitro safety profile, might serve as a basis for the development of novel treatments against serious infections. | ||
| + | |||
| + | Virtual Screening Approach and Investigation of Structure Activity Relationships to Discover Novel Bacterial Topoisomerase Inhibitors (NBTIs) Targeting Gram-Positive and Gram-Negative Pathogens.,Magaro' G, Prati F, Garofalo B, Corso G, Furlotti G, Apicella C, Mangano G, D'Atanasio N, Robinson D, Di Giorgio FP, Ombrato R J Med Chem. 2019 Jul 5. doi: 10.1021/acs.jmedchem.9b00394. PMID:31276392<ref>PMID:31276392</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6fm4" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Staan]] | ||
[[Category: Garofalo, B]] | [[Category: Garofalo, B]] | ||
[[Category: Mancini, F]] | [[Category: Mancini, F]] | ||
Revision as of 12:30, 17 July 2019
The crystal structure of S. aureus Gyrase complex with ID-130 and DNA
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Categories: Large Structures | Staan | Garofalo, B | Mancini, F | Mangano, G | Ombrato, R | Bacterial topoisomerase | Gyrase | Isomerase | Nbti
