View source for 2y66


==New 5-Benzylidenethiazolidine-4-one Inhibitors of Bacterial MurD Ligase: Design, Synthesis, Crystal Structures, and Biological Evaluation==
<StructureSection load='2y66' size='340' side='right'caption='[[2y66]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2y66]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli_K-12 Escherichia coli K-12]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Y66 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y66 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.49&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=KCX:LYSINE+NZ-CARBOXYLIC+ACID'>KCX</scene>, <scene name='pdbligand=N04:(2R)-2-[[3-[[3-[(Z)-(2,4-DIOXO-1,3-THIAZOLIDIN-5-YLIDENE)METHYL]PHENOXY]METHYL]PHENYL]CARBONYLAMINO]PENTANEDIOIC+ACID'>N04</scene>, <scene name='pdbligand=SO3:SULFITE+ION'>SO3</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=2y66 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y66 OCA], [https://pdbe.org/2y66 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y66 RCSB], [https://www.ebi.ac.uk/pdbsum/2y66 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y66 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/MURD_ECOLI MURD_ECOLI] Cell wall formation. Catalyzes the addition of glutamate to the nucleotide precursor UDP-N-acetylmuramoyl-L-alanine (UMA).[HAMAP-Rule:MF_00639]
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== Publication Abstract from PubMed ==
Mur ligases (MurC-MurF), a group of bacterial enzymes that catalyze four consecutive steps in the formation of cytoplasmic peptidoglycan precursor, are becoming increasingly adopted as targets in antibacterial drug design. Based on the crystal structure of MurD cocrystallized with thiazolidine-2,4-dione inhibitor I, we have designed, synthesized, and evaluated a series of improved glutamic acid containing 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD with IC(50) values up to 28muM. Inhibitor 37, with an IC(50) of 34muM, displays a weak antibacterial activity against S. aureus ATCC 29213 and E. faecalis ATCC 29212 with minimal inhibitory concentrations of 128mug/mL. High-resolution crystal structures of MurD in complex with two new inhibitors (compounds 23 and 51) reveal details of their binding modes within the active site and provide valuable information for further structure-based optimization.

New 5-benzylidenethiazolidin-4-one inhibitors of bacterial MurD ligase: Design, synthesis, crystal structures, and biological evaluation.,Zidar N, Tomasic T, Sink R, Kovac A, Patin D, Blanot D, Contreras-Martel C, Dessen A, Premru MM, Zega A, Gobec S, Masic LP, Kikelj D Eur J Med Chem. 2011 Sep 17. PMID:21963114<ref>PMID:21963114</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2y66" style="background-color:#fffaf0;"></div>

==See Also==
*[[Mur ligase|Mur ligase]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli K-12]]
[[Category: Large Structures]]
[[Category: Blanot D]]
[[Category: Contreras-Martel C]]
[[Category: Dessen A]]
[[Category: Gobec S]]
[[Category: Kikelj D]]
[[Category: Kovac A]]
[[Category: Muller-Premru M]]
[[Category: Patin D]]
[[Category: Peterlin-Masic L]]
[[Category: Sink R]]
[[Category: Tomasic T]]
[[Category: Zega A]]
[[Category: Zidar N]]