Computational Elucidation of Structural Basis for Ligand Binding with Mycobacterium tuberculosis Glucose-1-Phosphate Thymidylyltransferase (RmlA).

Computational Elucidation of Structural Basis for Ligand Binding with Mycobacterium tuberculosis Glucose-1-Phosphate Thymidylyltransferase (RmlA). Curr Pharm Biotechnol. 2016 Sep 9; Authors: Mansuri R, Ansari MY, Rana S, Singh J, Sinha S, Dikhit MR, Sahoo GC, Das P Abstract Glucose-1-Phosphate Thymidylyltransferase (RmlA) is one of the enzymes in rhamnose biosynthesis pathway, where rhamnose act as linker of peptidoglycan and arabinogalacton in the cell wall, therefore RmlA is a potential enzyme for the survival of Mycobacterium tuberculosis (Mtb). To go into the depth of the structure for exploring binding regions, homology model of RmlA was built in Prime, Schrodinger v9.2. The model with lowest Discrete Optimized Potential Energy (DOPE) score of -35524.17 kcal/mol and RMSD of 0.1 Å with the template (1H5R_B) was subjected to Molecular Dynamics Simulation (MDS) for 5 ns to achieve its stable folding state. The tertiary structure of the proposed model is composed of α/β/α sandwich type protein with quasi-Rossmann type folding pattern. The substrate, deoxy Thymidine tri phosphate (dTTP) comprises of triphosphate (R1) and methyl (R2) side chains where, R1 is highly essential for the survival of Mtb. Therefore, nineteen side chain analogues of dTTP were designed by substituting R1 and R2 chain of dTTP using Combi Glide, Schrodinger v9.2 and docked with the target RmlA protein. Out of which two analogues that is, 6-[(2R,3S,5R)-5-[5-...
Source: Current Pharmaceutical Biotechnology - Category: Biotechnology Authors: Tags: Curr Pharm Biotechnol Source Type: research