02569nas a2200397   4500000000100000008004100001260005100042653002700093653002200120653002400142653002300166653002100189653002300210653001600233653001800249653001200267653001400279653001100293653002100304653001200325653002200337653002800359653002500387653002200412653002000434653003300454653003300487653001900520100001600539700001600555245016100571300001200732490000700744520140600751022001402157       2012                            d  c2012 JunbSpringer Berlin / HeidelbergaBerlin10aAdenosine Triphosphate10aAmino Acid Motifs10aAmino Acid Sequence10aBacterial Proteins10aCatalytic Domain10aConserved Sequence10aDrug Design10aGlutamic Acid10aGlycine10aHistidine10aHumans10aHydrogen Bonding10aleprosy10aModels, Molecular10aMolecular Sequence Data10aMycobacterium leprae10aPeptide Synthases10aProtein Binding10aProtein Structure, Secondary10aStructural Homology, Protein10aThermodynamics1 aShanmugam A1 aNatarajan J00aHomology modeling and docking analyses of M. leprae Mur ligases reveals the common binding residues for structure based drug designing to eradicate leprosy.  a2659-720 v183 a<p>Multi drug resistance capacity for Mycobacterium leprae (MDR-Mle) demands the profound need for developing new anti-leprosy drugs. Since most of the drugs target a single enzyme, mutation in the active site renders the antibiotic ineffective. However, structural and mechanistic information on essential bacterial enzymes in a pathway could lead to the development of antibiotics that targets multiple enzymes. Peptidoglycan is an important component of the cell wall of M. leprae. The biosynthesis of bacterial peptidoglycan represents important targets for the development of new antibacterial drugs. Biosynthesis of peptidoglycan is a multi-step process that involves four key Mur ligase enzymes: MurC (EC:6.3.2.8), MurD (EC:6.3.2.9), MurE (EC:6.3.2.13) and MurF (EC:6.3.2.10). Hence in our work, we modeled the three-dimensional structure of the above Mur ligases using homology modeling method and analyzed its common binding features. The residues playing an important role in the catalytic activity of each of the Mur enzymes were predicted by docking these Mur ligases with their substrates and ATP. The conserved sequence motifs significant for ATP binding were predicted as the probable residues for structure based drug designing. Overall, the study was successful in listing significant and common binding residues of Mur enzymes in peptidoglycan pathway for multi targeted therapy.</p>  a0948-5023