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http://dx.doi.org/10.13160/ricns.2011.4.3.202

Comparative Modeling Studies of 1-deoxy-D-xylulose 5-phosphate Synthase (MEP pathway) from Mycobacterium Tuberculosis  

Kothandan, Gugan (Department of Biohemistry, Centre for Bioinformatics, University of Madras, Guindy campus)
Publication Information
Journal of Integrative Natural Science / v.4, no.3, 2011 , pp. 202-209 More about this Journal
Abstract
Tuberculosis is a major health problem in humans because of its multidrug resistance and discovering new treatments for this disease is urgently required. The synthesis of isoprenoids in Mycobacterium tuberculosis has been reported as an interesting pathway to target. In this context, 2C-methyl-D-erythritol 4-phosphate (MEP) pathway of M. tuberculosis has drawn attention. The MEP pathway begins with the condensation of glyceraldehyde 3-phosphate and pyruvate forming 1-deoxy-D-xylulose 5-phosphate (DXP) which is catalyzed by 1-deoxy-D-xylulose 5-phosphate synthase (DXS). As there is no X-ray structure was reported for this target, comparative modeling was used to generate the three dimensional structure. The structure was further validated by PROCHECK, VERIFY-3D, PROSA, ERRAT and WHATIF. Molecular docking studies was performed with the substrate (Thiamine pyrophosphate) and the reported inhibitor 2-methyl-3-(4-fluorophenyl)-5-(4-methoxy-phenyl)-4H-pyrazolol[1,5-a]pyrimidin-7-one) against the developed model to identify the crucial residues in the active site. This study may further be useful to provide structure based drug design.
Keywords
1-deoxy-D-xylulose 5-phosphate synthase (DXS); Homology Modeling; Molecular Docking; Drug Design; Tuberculosis;
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