Combination of site directed mutagenesis and secondary structure analysis predicts the amino acids essential for stability of M. leprae MurE.
The life-threatening infections caused by Mycobacterium leprae (Mle) remain a major challenge in developing countries as well as globe and there is a need to design potent anti-leprosy drugs. In our previous studies, ATP-dependent Mle-MurE ligase involved in biosynthesis of peptidoglycan was identified as one of the common drug targets, homology modeled and reported. In this work in silico site directed mutagenesis study was carried out on the homology modeled Mle-MurE ligase. This predicted the amino acids essential for stability. In addition, the distribution of these residues in different secondary structures and in active sites was analyzed. Finally, the role of the conserved residues in stability and function was analyzed. The availability of Mle-MurE ligase built model together with insights gained from stability studies and docking studies will promote the rational design of potent and selective Mle-MurE ligase inhibitors as anti-leprosy therapeutics.
Department of Bioinformatics, VMKV Engineering College, Vinayaka Missions University, Salem, 636308, India.
Anusuya
A
Shanmugam
Jeyakumar
J
Natarajan
D000255:Adenosine Triphosphate / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics*; D002384:Catalysis; D003198:Computer Simulation; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial; D006801:Humans; D007918:Leprosy / Q000188:drug therapy; D008024:Ligands; D016297:Mutagenesis, Site-Directed; D009166:Mycobacterium leprae / Q000378:metabolism*; D010453:Peptide Synthases / Q000737:chemistry* / Q000235:genetics*; D010457:Peptidoglycan / Q000737:chemistry; D017354:Point Mutation; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013816:Thermodynamics
D000596:Amino Acids; D001426:Bacterial Proteins; D008024:Ligands; D010457:Peptidoglycan; D000255:Adenosine Triphosphate; D010453:Peptide Synthases; C049145:UDP-N-acetylmuramoylalanyl-D-glutamate-2,6-diaminopimelate ligase