Crystallographic analyses of isoquinoline complexes reveal a new mode of metallo-β-lactamase inhibitionElectronic supplementary information (ESI) available: All experimental details, crystallographic data collection and refinement statistics, details of chemical synthesis, additional figures and tables. See DOI: 10.1039/c7cc02394d

Crystallographic analyses of the VIM-5 metallo-β-lactamase (MBL) with isoquinoline inhibitors reveal non zinc ion binding modes. Comparison with other MBL-inhibitor structures directed addition of a zinc-binding thiol enabling identification of potent B1 MBL inhibitors. The inhibitors potentiate meropenem activity against clinical isolates harboring MBLs. Crystallographic analyses revealed new metallo β-lactamase inhibition modes and enable the design of potent zinc-binding inhibitors.