Structural highlights
Function
[RMLC_MYCTU] Catalyzes the epimerization of the C3' and C5'positions of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4-hexulose. Involved in the biosynthesis of the dTDP-L-rhamnose which is a component of the critical linker, D-N-acetylglucosamine-L-rhamnose disaccharide, which connects the galactan region of arabinogalactan to peptidoglycan via a phosphodiester linkage.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Li W, Xin Y, McNeil MR, Ma Y. rmlB and rmlC genes are essential for growth of mycobacteria. Biochem Biophys Res Commun. 2006 Mar 31;342(1):170-8. Epub 2006 Feb 3. PMID:16472764 doi:http://dx.doi.org/10.1016/j.bbrc.2006.01.130
- ↑ Babaoglu K, Page MA, Jones VC, McNeil MR, Dong C, Naismith JH, Lee RE. Novel inhibitors of an emerging target in Mycobacterium tuberculosis; substituted thiazolidinones as inhibitors of dTDP-rhamnose synthesis. Bioorg Med Chem Lett. 2003 Oct 6;13(19):3227-30. PMID:12951098
