View source for 3zei


==Structure of the Mycobacterium tuberculosis O-Acetylserine Sulfhydrylase (OASS) CysK1 in complex with a small molecule inhibitor==
<StructureSection load='3zei' size='340' side='right'caption='[[3zei]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zei]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZEI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZEI 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]] 2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AWH:3-[(Z)-[(5Z)-5-[[2-(2-HYDROXY-2-OXOETHYLOXY)PHENYL]METHYLIDENE]-3-METHYL-4-OXIDANYLIDENE-1,3-THIAZOLIDIN-2-YLIDENE]AMINO]BENZOIC+ACID'>AWH</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</scene>, <scene name='pdbligand=PLP:PYRIDOXAL-5-PHOSPHATE'>PLP</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=3zei FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zei OCA], [https://pdbe.org/3zei PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zei RCSB], [https://www.ebi.ac.uk/pdbsum/3zei PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zei ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CYSK_MYCTU CYSK_MYCTU] Catalyzes the conversion of O-acetylserine (OAS) to cysteine through the elimination of acetate and addition of hydrogen sulfide.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cysteine biosynthetic pathway is absent in humans but essential in microbial pathogens, suggesting that it provides potential targets for the development of novel antibacterial compounds. CysK1 is a pyridoxalphosphate-dependent O-acetyl sulfhydrylase, which catalyzes the formation of L-cysteine from O-acetyl serine and hydrogen sulfide. Here we report nanomolar thiazolidine inhibitors of M. tuberculosis CysK1 developed by rational inhibitor design. The thiazolidine compounds were discovered using the crystal structure of a CysK1-peptide inhibitor complex as template. Pharmacophore modelling and subsequent in vitro screening gave an initial hit compound 2 (IC50 of 103.8 nM) which was subsequently optimized by a combination of protein crystallography, modelling, and synthetic chemistry. Hit expansion of 2 by chemical synthesis led to improved thiazolidine inhibitors with an IC50 value of 19 nM for the best compound, a 150 fold higher potency than the natural peptide inhibitor (IC50 2.9 microM).

Structure-Guided Design of Novel Thiazolidine Inhibitors of O-Acetyl Serine Sulfhydrylase from Mycobacterium tuberculosis.,Poyraz O, Jeankumar VU, Saxena S, Schnell R, Haraldsson M, Yogeeswari P, Sriram D, Schneider G J Med Chem. 2013 Jul 23. PMID:23879381<ref>PMID:23879381</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3zei" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Poyraz O]]
[[Category: Schneider G]]
[[Category: Schnell R]]