title: Computational studies on the resistance of penicillin-binding protein 2B (PBP2B) of wild-type and mutant strains of Streptococcus pneumoniae against β-lactam antibiotics.
abstract: Mutations within transpeptidase domain of penicillin-binding protein 2B of the strains of Streptococcus pneumoniae leads to resistance against β-lactam antibiotics. To uncover the important residues responsible for sensitivity and resistance, the recently determined three dimensional structures of penicillin-binding protein 2B of both wild-type R6 (sensitive) and mutant 5204 (resistant) strains along with the predicted structures of other mutant strains G54, Hungary19A-6 and SP195 were considered for the interaction study with β-lactam antibiotics using induced-fit docking of Schrödinger. Associated binding energies of the complexes and their intermolecular interactions in the binding site clearly show that the wild-type R6 as sensitive, mutant strains 5204 and G54 as highly resistant, and the mutant strains Hungary19A-6 and SP195 as intermediate resistant. The study also reveals that the mutant strains Hungary19A-6 and SP195 exhibit intermediate resistant because of the existence of mutations till the intermediate 538th and 516th positions, respectively, and not till the end of the C-terminus. Furthermore, our investigations show that if the mutations are extended till the end of the C terminus, then the antibiotic resistance of induced-mutated strains increases from intermediate to high as in the strains 5204 and G54. The binding patterns obtained in the study are useful in designing potential inhibitors against multidrug resistant S. pneumoniae.
authors.affiliation: Department of Bioinformatics, School of Life Sciences, Bharathidasan University, Tiruchirappalli 620 024, Tamil Nadu, IndiaDepartment of Zoology, Dharmapuram Gnanambigai Government Arts College (Women), Mayiladuthurai 609 001, Tamil Nadu, IndiaDepartment of Bioinformatics, School of Biotechnology and Health Sciences, Karunya University, Coimbatore 641 114, Tamil Nadu, India.
authors.forename: Jothi
authors.initials: J
authors.lastname: Ramalingam
authors.forename: Jannet
authors.initials: J
authors.lastname: Vennila
authors.forename: Parthasarathy
authors.initials: P
authors.lastname: Subbiah
mesh_terms: D000595:Amino Acid Sequence; D019881:Aminoacyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D009154:Mutation; D046915:Penicillin-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013816:Thermodynamics; D047090:beta-Lactams / Q000378:metabolism / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D046915:Penicillin-Binding Proteins; D047090:beta-Lactams; D019881:Aminoacyltransferases; C478701:penicillin-binding protein 2b, Streptococcus