title: Inhibiting the VIM-2 Metallo-β-Lactamase by Graphene Oxide and Carbon Nanotubes.
abstract: Metallo-β-lactamases (MBLs) degrade a broad spectrum of antibiotics including the latest carbapenems. So far, limited success has been achieved in developing its inhibitors using small organic molecules. VIM-2 is one of the most studied and important MBLs. In this work, we screened 10 nanomaterials, covering a diverse range of surface properties including charge, hydrophobicity, and specific chemical bonding. Among these, graphene oxide and carbon nanotubes are the most potent inhibitors, while most other materials do not show much inhibition effect. The inhibition is noncompetitive and is attributed to the hydrophobic interaction with the enzyme. Adsorption of VIM-2 was further probed using protein displacement assays where it cannot displace or be displaced by bovine serum albumin (BSA). This information is useful for rational design inhibitors for MBLs and more specific inhibition might be achieved by further surface modifications on these nanocarbons.
authors.affiliation: Department of Chemistry, Waterloo Institute for Nanotechnology University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
authors.forename: Po-Jung Jimmy
authors.initials: PJ
authors.lastname: Huang
authors.affiliation: Department of Chemistry, Waterloo Institute for Nanotechnology University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
authors.forename: Rachel
authors.initials: R
authors.lastname: Pautler
authors.affiliation: Department of Chemistry, Waterloo Institute for Nanotechnology University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
authors.forename: Jenitta
authors.initials: J
authors.lastname: Shanmugaraj
authors.affiliation: Department of Chemistry, Waterloo Institute for Nanotechnology University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Labbé
authors.affiliation: Department of Chemistry, Waterloo Institute for Nanotechnology University of Waterloo, Waterloo, Ontario, Canada N2L 3G1.
authors.forename: Juewen
authors.initials: J
authors.lastname: Liu
mesh_terms: D000327:Adsorption; D000818:Animals; D002417:Cattle; D002511:Cephalosporins / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006108:Graphite / Q000494:pharmacology; D006868:Hydrolysis; D007700:Kinetics; D049329:Nanostructures; D037742:Nanotubes, Carbon / Q000737:chemistry*; D010087:Oxides / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D015032:Zinc / Q000494:pharmacology; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D002511:Cephalosporins; D004791:Enzyme Inhibitors; D037742:Nanotubes, Carbon; D010087:Oxides; D012710:Serum Albumin, Bovine; D012965:Sodium Chloride; D006108:Graphite; C425108:beta-lactamase bla(vim-2); D001618:beta-Lactamases; C021720:nitrocefin; D015032:Zinc
keywords: adsorption; beta-lactamases; carbon nanotubes; graphene; inhibition; nanomaterials