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3zei

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{{STRUCTURE_3zei| PDB=3zei | SCENE= }}
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==Structure of the Mycobacterium tuberculosis O-Acetylserine Sulfhydrylase (OASS) CysK1 in complex with a small molecule inhibitor==
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===Structure of the Mycobacterium tuberculosis O-Acetylserine Sulfhydrylase (OASS) CysK1 in complex with a small molecule inhibitor===
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<StructureSection load='3zei' size='340' side='right' caption='[[3zei]], [[Resolution|resolution]] 2.00&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23879381}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3zei]] is a 1 chain structure with sequence from [http://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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZEI FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cysteine_synthase Cysteine synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.5.1.47 2.5.1.47] </span></td></tr>
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<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=3zei FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zei OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zei RCSB], [http://www.ebi.ac.uk/pdbsum/3zei PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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).
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==Function==
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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>
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[[http://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.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3zei]] is a 1 chain structure with sequence from [http://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].
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</div>
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:023879381</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Cysteine synthase]]
[[Category: Cysteine synthase]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
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[[Category: Poyraz, O.]]
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[[Category: Poyraz, O]]
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[[Category: Schneider, G.]]
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[[Category: Schneider, G]]
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[[Category: Schnell, R.]]
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[[Category: Schnell, R]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]
[[Category: Inhibitor]]
[[Category: Inhibitor]]

Revision as of 09:11, 21 December 2014

Structure of the Mycobacterium tuberculosis O-Acetylserine Sulfhydrylase (OASS) CysK1 in complex with a small molecule inhibitor

3zei, resolution 2.00Å

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