4mb9

<StructureSection load='4mb9' size='340' side='right' caption='[[4mb9]], [[Resolution|resolution]] 1.85&Aring;' scene=''>

<table><tr><td colspan='2'>[[4mb9]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Streptococcus_pneumoniae_ga47373 Streptococcus pneumoniae ga47373]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MB9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MB9 FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=28F:1-ETHYL-3-{6-(PYRIMIDIN-5-YL)-5-[(3R)-TETRAHYDROFURAN-3-YLMETHOXY][1,3]THIAZOLO[5,4-B]PYRIDIN-2-YL}UREA'>28F</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SPAR94_0831 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=760835 Streptococcus pneumoniae GA47373])</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=4mb9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mb9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mb9 RCSB], [http://www.ebi.ac.uk/pdbsum/4mb9 PDBsum]</span></td></tr>

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== Publication Abstract from PubMed ==

A pharmacophore-based search led to the identification of thiazolopyridine ureas as a novel scaffold with antitubercular activity acting through inhibition of DNA Gyrase B (GyrB) ATPase. Evaluation of the binding mode of thiazolopyridines in a Mycobacterium tuberculosis (Mtb) GyrB homology model prompted exploration of side-chains at the thiazolopyridine ring C-5 position to access the ribose/solvent pocket. Potent compounds with GyrB IC50 &lt;/=1 nM and Mtb MIC &lt;/=0.1 microM were obtained with certain combinations of side-chains at C-5 position and heterocycles at C-6 position of the thiazolopyridine core. Substitutions at C-5 also enabled optimization of physicochemical properties. Representative compounds were co-crystallized with Streptococcus pneumoniae (Spn) ParE; these confirmed the binding modes predicted by the homology model. The target link to GyrB was confirmed by genetic mapping of mutations conferring resistance to thiazolopyridine ureas. The compounds are bactericidal in vitro and efficacious in vivo in an acute murine model of tuberculosis.

Thiazolopyridine Ureas as Novel Antitubercular Agents Acting Through Inhibition of DNA Gyrase B.,Ghorpade SR, Kale M, Raichurkar A, Hameed P S, Waterson D, McKinney D, Mramaiah M, Koushik K, Jena LK, Shinde V, Rudrapatna S, Humnabadkar V, Madhavapeddi P, Basavarajappa H, Ghosh A, Murthy R, Guptha S, Sharma S, Vachaspati P, K N MK, Giridhar J, Reddy J, Panduga V, Ganguly S, Ahuja V, Gaonkar S, C N NK, Ogg D, Tucker JA, Boriack-Sjodin PA, de Sousa SM, Sambandamurthy V, Kranthi U, Barde S J Med Chem. 2013 Oct 3. PMID:24088190<ref>PMID:24088190</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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*[[Topoisomerase|Topoisomerase]]

[[Category: Streptococcus pneumoniae ga47373]]

[[Category: Ogg, D]]

[[Category: Tucker, J]]

[[Category: Antimicrobial]]

[[Category: Structure-based drug design]]