Probing the Interaction of Aspergillomarasmine A with Metallo-β-lactamases NDM-1, VIM-2, and IMP-7 Journal Articles uri icon

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  • Metallo-β-lactamases (MBLs) are a growing threat to the continued efficacy of β-lactam antibiotics. Recently, aspergillomarasmine A (AMA) was identified as an MBL inhibitor, but the mode of inhibition was not fully characterized. Equilibrium dialysis and metal analysis studies revealed that 2 equiv of AMA effectively removes 1 equiv of Zn(II) from MBLs NDM-1, VIM-2, and IMP-7 when the MBL is at micromolar concentrations. Conversely, 1H NMR studies revealed that 2 equiv of AMA remove 2 equiv of Co(II) from Co(II)-substituted NDM-1, VIM-2, and IMP-7 when the MBL/AMA are at millimolar concentrations. Our findings reveal that AMA inhibits the MBLs by removal of the active site metal ions required for β-lactam hydrolysis among the most clinically significant MBLs.


  • Bergstrom, Alexander
  • Katko, Andrew
  • Adkins, Zach
  • Hill, Jessica
  • Cheng, Zishuo
  • Burnett, Mia
  • Yang, Hao
  • Aitha, Mahesh
  • Mehaffey, M Rachel
  • Brodbelt, Jennifer S
  • Tehrani, Kamaleddin HME
  • Martin, Nathaniel I
  • Bonomo, Robert A
  • Page, Richard C
  • Tierney, David L
  • Fast, Walter
  • Wright, Gerard
  • Crowder, Michael W

publication date

  • February 9, 2018