View source for 2y76


==Structure of Mycobacterium tuberculosis type II dehydroquinase complexed with (1R,4S,5R)-3-(benzo(b)thiophen-5-ylmethoxy)-2-(benzo(b) thiophen-5-ylmethyl)-1,4,5-trihydroxycyclohex-2-enecarboxylate==
<StructureSection load='2y76' size='340' side='right'caption='[[2y76]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2y76]] 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=2Y76 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Y76 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]] 2.5&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CB7:(1R,4S,5R)-3-(BENZO[B]THIOPHEN-5-YL)METHOXY-2-(BENZO[B]THIOPHEN-5-YL)METHYL-1,4,5-TRIHYDROXYCYCLOHEX-2-ENE-1-CARBOXYLATE'>CB7</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=2y76 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2y76 OCA], [https://pdbe.org/2y76 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2y76 RCSB], [https://www.ebi.ac.uk/pdbsum/2y76 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2y76 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/AROQ_MYCTU AROQ_MYCTU] Catalyzes a trans-dehydration via an enolate intermediate (By similarity).[HAMAP-Rule:MF_00169]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The synthesis of high-affinity reversible competitive inhibitors of Mycobacterium tuberculosis type II dehydroquinase, an essential enzyme in Mycobacterium tuberculosis bacteria, is reported. The inhibitors reported here are mimics of the enol intermediate and the effect of substitution on C2 was studied. The crystal structures of Mycobacterium tuberculosis type II dehydroquinase in complex with three of the reported inhibitors are also described. The results show that an aromatic substituent on C2 prevents the closure of the active site by impeding the hydrogen-bonding interaction of Arg108 with the essential Tyr24 of the flexible loop, the residue that initiates catalysis. Chemical modifications of the reported acids were also carried out to improve internalization into Mycobacterium tuberculosis through an ester prodrug approach. Propyl esters proved to be the most efficient in achieving optimal in vitro activities.

A Prodrug Approach for Improving Antituberculosis Activity of Potent Mycobacterium tuberculosis Type II Dehydroquinase Inhibitors.,Tizon L, Otero JM, Prazeres VF, Llamas-Saiz AL, Fox GC, van Raaij MJ, Lamb H, Hawkins AR, Ainsa JA, Castedo L, Gonzalez-Bello C J Med Chem. 2011 Aug 3. PMID:21780742<ref>PMID:21780742</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2y76" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dehydroquinase 3D structures|Dehydroquinase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Ainsa JA]]
[[Category: Castedo L]]
[[Category: Fox GC]]
[[Category: Gonzalez-Bello C]]
[[Category: Hawkins AR]]
[[Category: Lamb H]]
[[Category: Llamas-Saiz AL]]
[[Category: Otero JM]]
[[Category: Prazeres VFV]]
[[Category: Tizon L]]
[[Category: Van Raaij MJ]]