Research

When searching for new inhibitors we have successfully screened 500 fragments, which are parts of a future inhibitor, and found hits inhibiting VIM-2 (a MBL) or NDM-1 (a MBL) or OXA-48 (a SBL). These fragments will be grown into bigger molecules with more atoms, aiming for better inhibitor properties. During the inhibitor design, we use the solved crystal structures of our drug targets, since the new inhibitors should fit into these enzymes.

We are a part of The Norwegian Structural Biology Centre (NorStruct), at UiT The Arctic University of Norway. 

So far, we have successfully solved for several new metallo-ß-lactamases crystal structures, including MYO-1, ECV-1, TMB-1, VIM-7, AIM-1, GIM-1 and VIM-26. And also VIM-2 and OXA-48 in complex with fragments.  

Currently used methods:

Protein crystallography Structure activity relationships (SAR) for: Mutants, Substrates and inhibitors Surface plasmon resonance (SPR)  In silico modelling of new inhibitors Biochemical characterization towards substrates Biochemical characterization with inhibitors including: Dose-rate determination to obtain IC50 values Whole cell experiments with and without inhibitors Minimal Inhibitory Concentration (MIC) in collaboration with K-res, UNN.