1PM7

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

Summary for 1PM7

• Entry DOI: 10.2210/pdb1pm7/pdb
• Descriptor: RFBC, ACETATE ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: rmlc, beta barrel, main beta sheet structure, structural genomics, psi, protein structure initiative, tb structural genomics consortium, tbsgc, isomerase
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 2
• Total formula weight: 44976.17

Authors

Dong, C.,Naismith, J.H.,TB Structural Genomics Consortium (TBSGC) (deposition date: 2003-06-10, release date: 2003-12-09, Last modification date: 2024-02-14)

Primary citation

Babaoglu, K.,Page, M.A.,Jones, V.C.,McNeil, M.R.,Dong, C.,Naismith, J.H.,Lee, R.E.
Novel inhibitors of an emerging target in Mycobacterium tuberculosis; substituted thiazolidinones as inhibitors of dTDP-rhamnose synthesis.
Bioorg.Med.Chem.Lett., 13:3227-3230, 2003

PubMed Abstract: 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.

PubMed: 12951098
DOI: 10.1016/S0960-894X(03)00673-5

Experimental method

X-RAY DIFFRACTION (2.2 Å)