2y77

Structure of Mycobacterium tuberculosis type II dehydroquinase complexed with (1R,4S,5R)-3-(benzo(b)thiophen-2-ylmethoxy)-1,4,5- trihydroxy-2-(thiophen-2-ylmethyl)cyclohex-2-enecarboxylate

spinqualitylabelsall models 2y77, resolution 1.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2y77 is a 1 chain structure with sequence from "bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CB8, SO4 Related: 1h0r, 2xb8, 2y71, 1h05, 2dhq, 1h0s, 2y76 Activity: 3-dehydroquinate dehydratase, with EC number 4.2.1.10 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [AROQ_MYCTU] Catalyzes a trans-dehydration via an enolate intermediate (By similarity).[HAMAP-Rule:MF_00169] 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Dehydroquinase 3D structures

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