View source for 3saz


==Crystal structure of Mycobacterium tuberculosis malate synthase in complex with 4-(3-bromophenyl)-2,4-dioxobutanoic acid inhibitor==
<StructureSection load='3saz' size='340' side='right'caption='[[3saz]], [[Resolution|resolution]] 2.04&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3saz]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3SAZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3SAZ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=043:4-(3-BROMOPHENYL)-2,4-DIOXOBUTANOIC+ACID'>043</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1n8i|1n8i]], [[1n8w|1n8w]], [[2gq3|2gq3]], [[3s9i|3s9i]], [[3s9z|3s9z]], [[3sad|3sad]], [[3sb0|3sb0]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">glcB, GlcB (Rv1837c), MT1885, MTCY1A11.06, Rv1837c ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 "Bacillus tuberculosis" (Zopf 1883) Klein 1884])</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Malate_synthase Malate synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.9 2.3.3.9] </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=3saz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3saz OCA], [https://pdbe.org/3saz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3saz RCSB], [https://www.ebi.ac.uk/pdbsum/3saz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3saz ProSAT]</span></td></tr>
</table>
== Function ==
[[https://www.uniprot.org/uniprot/MASZ_MYCTU MASZ_MYCTU]] Involved in the glycolate utilization. Catalyzes the condensation and subsequent hydrolysis of acetyl-coenzyme A (acetyl-CoA) and glyoxylate to form malate and CoA (By similarity).[HAMAP-Rule:MF_00641] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The glyoxylate shunt plays an important role in fatty acid metabolism and has been shown to be critical to survival of several pathogens involved in chronic infections. For Mycobacterium tuberculosis (Mtb), a strain with a defective glyoxylate shunt was previously shown to be unable to establish infection in a mouse model. We report the development of phenyl-diketo acid (PDKA) inhibitors of malate synthase (GlcB), one of two glyoxylate shunt enzymes, using structure-based methods. PDKA inhibitors were active against Mtb grown on acetate, and overexpression of GlcB ameliorated this inhibition. Crystal structures of complexes of GlcB with PDKA inhibitors guided optimization of potency. A selected PDKA compound demonstrated efficacy in a mouse model of tuberculosis. The discovery of these PDKA derivatives provides chemical validation of GlcB as an attractive target for tuberculosis therapeutics.

Structure-guided discovery of phenyl-diketo acids as potent inhibitors of M. tuberculosis malate synthase.,Krieger IV, Freundlich JS, Gawandi VB, Roberts JP, Gawandi VB, Sun Q, Owen JL, Fraile MT, Huss SI, Lavandera JL, Ioerger TR, Sacchettini JC Chem Biol. 2012 Dec 21;19(12):1556-67. doi: 10.1016/j.chembiol.2012.09.018. PMID:23261599<ref>PMID:23261599</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3saz" style="background-color:#fffaf0;"></div>

==See Also==
*[[Malate synthase 3D structures|Malate synthase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Malate synthase]]
[[Category: Krieger, I V]]
[[Category: Sacchettini, J C]]
[[Category: Sun, Q]]
[[Category: XMTB, Mycobacterium Tuberculosis Structural Proteomics Project]]
[[Category: Inhibitor complex]]
[[Category: Mycobacterium tuberculosis structural proteomics project]]
[[Category: Structural genomic]]
[[Category: Transferase-transferase inhibitor complex]]
[[Category: Xmtb]]