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| | ==Structure of Streptococcus pneumonia pare in complex with AZ13072886== | | ==Structure of Streptococcus pneumonia pare in complex with AZ13072886== |
| - | <StructureSection load='4mot' size='340' side='right' caption='[[4mot]], [[Resolution|resolution]] 1.75Å' scene=''> | + | <StructureSection load='4mot' size='340' side='right'caption='[[4mot]], [[Resolution|resolution]] 1.75Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4mot]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Strr6 Strr6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MOT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MOT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4mot]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Streptococcus_pneumoniae_R6 Streptococcus pneumoniae R6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MOT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4MOT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2B7:1-[4-(3-METHYLBUTYL)-5-OXO-6-(PYRIDIN-3-YL)-4,5-DIHYDRO[1,3]THIAZOLO[5,4-B]PYRIDIN-2-YL]-3-PROP-2-EN-1-YLUREA'>2B7</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=2B7:1-[4-(3-METHYLBUTYL)-5-OXO-6-(PYRIDIN-3-YL)-4,5-DIHYDRO[1,3]THIAZOLO[5,4-B]PYRIDIN-2-YL]-3-PROP-2-EN-1-YLUREA'>2B7</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4em7|4em7]], [[4emv|4emv]], [[4mbc|4mbc]], [[4mb9|4mb9]]</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=4mot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mot OCA], [https://pdbe.org/4mot PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4mot RCSB], [https://www.ebi.ac.uk/pdbsum/4mot PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4mot ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">parE, spar94_0831, spr0756 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=171101 STRR6])</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=4mot FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mot OCA], [http://pdbe.org/4mot PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mot RCSB], [http://www.ebi.ac.uk/pdbsum/4mot PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mot ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/Q8DQB5_STRR6 Q8DQB5_STRR6] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4mot" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4mot" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Topoisomerase 3D structures|Topoisomerase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Strr6]] | + | [[Category: Large Structures]] |
| - | [[Category: Boriack-Sjodin, P A]] | + | [[Category: Streptococcus pneumoniae R6]] |
| - | [[Category: Ogg, D]] | + | [[Category: Boriack-Sjodin PA]] |
| - | [[Category: Antimicrobial]]
| + | [[Category: Ogg D]] |
| - | [[Category: Atp binding]]
| + | |
| - | [[Category: Isomerase-isomerase inhibitor complex]]
| + | |
| - | [[Category: Structure-based drug design]] | + | |
| - | [[Category: Virtual screen]]
| + | |
| Structural highlights
Function
Q8DQB5_STRR6
Publication Abstract from PubMed
Scaffold hopping from the thiazolopyridine ureas led to thiazolopyridone ureas with potent antitubercular activity acting through inhibition of DNA GyrB ATPase activity. Structural diversity was introduced, by extension of substituents from the thiazolopyridone N-4 position, to access hydrophobic interactions in the ribose pocket of the ATP binding region of GyrB. Further optimization of hydrogen bond interactions with arginines in site-2 of GyrB active site pocket led to potent inhibition of the enzyme (IC50 2nM) along with potent cellular activity (MIC=0.1muM) against Mycobacterium tuberculosis (Mtb). Efficacy was demonstrated in an acute mouse model of tuberculosis on oral administration.
Thiazolopyridone ureas as DNA gyrase B inhibitors: Optimization of antitubercular activity and efficacy.,Kale RR, Kale MG, Waterson D, Raichurkar A, Hameed SP, Manjunatha MR, Kishore Reddy BK, Malolanarasimhan K, Shinde V, Koushik K, Jena LK, Menasinakai S, Humnabadkar V, Madhavapeddi P, Basavarajappa H, Sharma S, Nandishaiah R, Mahesh Kumar KN, Ganguly S, Ahuja V, Gaonkar S, Naveen Kumar CN, Ogg D, Boriack-Sjodin PA, Sambandamurthy VK, de Sousa SM, Ghorpade SR Bioorg Med Chem Lett. 2014 Feb 1;24(3):870-9. doi: 10.1016/j.bmcl.2013.12.080., Epub 2013 Dec 25. PMID:24405701[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kale RR, Kale MG, Waterson D, Raichurkar A, Hameed SP, Manjunatha MR, Kishore Reddy BK, Malolanarasimhan K, Shinde V, Koushik K, Jena LK, Menasinakai S, Humnabadkar V, Madhavapeddi P, Basavarajappa H, Sharma S, Nandishaiah R, Mahesh Kumar KN, Ganguly S, Ahuja V, Gaonkar S, Naveen Kumar CN, Ogg D, Boriack-Sjodin PA, Sambandamurthy VK, de Sousa SM, Ghorpade SR. Thiazolopyridone ureas as DNA gyrase B inhibitors: Optimization of antitubercular activity and efficacy. Bioorg Med Chem Lett. 2014 Feb 1;24(3):870-9. doi: 10.1016/j.bmcl.2013.12.080., Epub 2013 Dec 25. PMID:24405701 doi:http://dx.doi.org/10.1016/j.bmcl.2013.12.080
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