Structure, evolution and virtual screening of NDM-1 strain from Kolkata

Int J Bioinform Res Appl. 2014;10(3):235-63. doi: 10.1504/IJBRA.2014.060761.

Abstract

β-lactam antibiotics are utilised to treat bacterial infection. β-lactamase enzymes (EC 3.5.2.6) are produced by several bacteria and are responsible for their resistance to β-lactam antibiotics like penicillin, cephamycins and carbapenems. New Delhi Metallo-β-lactamase (NDM-1) is a gene that makes bacteria resistant to β-lactam antibiotics. Preparing a compound against NDM-1 will require additional investment and development by drug manufacturers as the current antibiotics will not treat patients with NDM-1 resistance. NDM-1 of Kolkata showed convergent-type evolution with other NDM-1 producing strains. The modelled structure exhibited α-β-α barrel-type domain along with Zn metallo-β-lactamase N-terminal domain. Compounds belonging to cephalosporins (relatively resistant to β-lactamase) and other antibiotics ceftaroline, ceftobiprole, piperacillin, penamecillin, azidocillin, cefonicid, tigecycline and colistin have exhibited better binding affinity with the modelled NDM-1.

Keywords: NDM–1 evolution; NDM–1 resistance; NDM–1 structure; alpha–beta–alpha barrel; antibiotics; azidocillin; beta–lactamase enzymes; carbapenems; cefonicid; ceftaroline; ceftobiprole; cephalosporins; cephamycins; colistin; modelling; penamecillin; penicillin; piperacillin; threading; tigecycline; virtual screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis*
  • Binding Sites
  • Computer Simulation
  • Drug Design*
  • Drug Evaluation, Preclinical / methods*
  • Enzyme Inhibitors / chemical synthesis
  • Evolution, Molecular*
  • Models, Chemical*
  • beta-Lactamases / chemistry*
  • beta-Lactamases / genetics*
  • beta-Lactamases / ultrastructure

Substances

  • Anti-Bacterial Agents
  • Enzyme Inhibitors
  • beta-Lactamases
  • beta-lactamase NDM-1