In silico and Mass Spectrometric Characterization of Hpa2-ACO-Kan ternary complex of MDR Acinetobacter baumannii
Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba-400 005, 1UM-DAE Centre for Excellence in Basic Sciences, Mumbai University Campus, Kalina, Santa Cruz-400 098, Mumbai, India
UM-DAE Centre for Excellence in Basic Sciences, Mumbai University Campus, Kalina, Santa Cruz-400 098, Mumbai, India, E-mail: [email protected]
Inactivation of antibiotics by enzymatic acetylation is considered as one of the major resistance mechanisms. Transfer of acetyl group to aminoglycoside antibiotics involved formation of a ternary complex. The acetyl- CoA-Hpa2-polyamine/antibiotic ternary complex was studied using in silico and mass spectrometric methods. Molecular interactions involved in the formation and stabilization of the ternary complex were analysed. To identify the amino acids necessary for stabilization of the ternary complex and to study the overall protein thermodynamic stability, FoldX algorithm was used. Results attested that Hpa2 has capacity to form stable ternary complex with acetyl-CoA and polyamines (spermine, spermidine, putrescine) or aminoglycoside antibiotics (kanamycin, streptomycin). This is the fi rst experimental report showing acetyl-CoA-Hpa2- kanamycin ternary complex and formation of this ternary complex is important for its function.