TY - JOUR
AU - Shanmugam A
AU - Natarajan J
AB - 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.
BT - Interdisciplinary sciences, computational life sciences
C1 - http://www.ncbi.nlm.nih.gov/pubmed/24464703?dopt=Abstract
DA - 2014 Mar
DO - 10.1371/journal.pntd.0002845
IS - 1
J2 - Interdiscip Sci
LA - eng
N2 - 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.
PY - 2014
SP - 40
EP - 7
T2 - Interdisciplinary sciences, computational life sciences
TI - Combination of site directed mutagenesis and secondary structure analysis predicts the amino acids essential for stability of M. leprae MurE.
VL - 6
SN - 1867-1462
ER -