Inhibitor discovery of full-length New Delhi metallo-β-lactamase-1 (NDM-1).
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 23675445.
- Also identified by DOI 10.1371/journal.pone.0062955 and PMC identifier 3652859.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
New Delhi metallo-β-lactmase-1 (NDM-1) has recently attracted extensive attention for its biological activities to catalyze the hydrolysis of almost all of β-lactam antibiotics. To study the catalytic property of NDM-1, the steady-kinetic parameters of NDM-1 toward several kinds of β-lactam antibiotics have been detected. It could effectively hydrolyze most β-lactams (k cat/K m ratios between 0.03 to 1.28 µmol⁻¹.s⁻¹), except aztreonam. We also found that thiophene-carboxylic acid derivatives could inhibit NDM-1 and have shown synergistic antibacterial activity in combination with meropenem. Flexible docking and quantum mechanics (QM) study revealed electrostatic interactions between the sulfur atom of thiophene-carboxylic acid derivatives and the zinc ion of NDM-1, along with hydrogen bond between inhibitor and His189 of NDM-1. The interaction models proposed here can be used in rational design of NDM-1 inhibitors.
Medical subject headings
- Anti-Bacterial Agents
- Aztreonam
- Bacterial Proteins
- Enzyme Inhibitors
- Escherichia coli
- Thienamycins
- beta-Lactamase Inhibitors
- beta-Lactams