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spinqualitylabelsall models 1pm7, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

RmlC (dTDP-6-DEOXY-D-XYLO-4-HEXULOSE 3,5-EPIMERASE)STRUCTURE FROM MYCOBACTERIUM TUBERCULOSIS AND INHIBITOR DESIGN. THE APO STRUCTURE.

Overview

The emergence of multi-drug resistant tuberculosis, coupled with the, increasing overlap of the AIDS and tuberculosis pandemics has brought, tuberculosis to the forefront as a major worldwide health concern. In an, attempt to find new inhibitors of the enzymes in the essential rhamnose, biosynthetic pathway, a virtual library of 2,3,5, trisubstituted-4-thiazolidinones was created. These compounds were then, docked into the active site cavity of 6'hydroxyl;, dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase (RmlC) from Mycobacterium, tuberculosis. The resulting docked conformations were consensus scored and, the top 5% were slated for synthesis. Thus far, 94 compounds have been, successfully synthesized and initially tested. Of those, 30 (32%) have >, or =50% inhibitory activity (at 20 microM) in the coupled rhamnose, synthetic assay with seven of the 30 also having modest activity against, whole-cell M. tuberculosis.

About this Structure

1PM7 is a Single protein structure of sequence from Mycobacterium tuberculosis with ACT and GOL as ligands. Active as dTDP-4-dehydrorhamnose 3,5-epimerase, with EC number 5.1.3.13 Full crystallographic information is available from OCA.

Reference

Novel inhibitors of an emerging target in Mycobacterium tuberculosis; substituted thiazolidinones as inhibitors of dTDP-rhamnose synthesis., Babaoglu K, Page MA, Jones VC, McNeil MR, Dong C, Naismith JH, Lee RE, Bioorg Med Chem Lett. 2003 Oct 6;13(19):3227-30. PMID:12951098

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