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See detailAllosteric inhibition of VIM metallo-beta-lactamase by a camelid nanobody
Sohier, Jean ULg; Laurent, Clémentine ULg; Chevigné, Andy et al

in Biochemical Journal (2013), 450(3), 477-486

Metallo-β-lactamase (MβL) enzymes are usually produced by multiresistant Gram-negative bacterial strains and have spread worldwide. An approach based on phage display was employed to select single-domain ... [more ▼]

Metallo-β-lactamase (MβL) enzymes are usually produced by multiresistant Gram-negative bacterial strains and have spread worldwide. An approach based on phage display was employed to select single-domain antibody fragments (VHHs also called Nanobodies) that would inhibit the clinically relevant VIM-4 MβL. Out of more than 50 selected nanobodies, only the NbVIM_38 nanobody inhibited VIM-4. The paratope, inhibition mechanism and epitope of NbVIM_38 nanobody were then characterised. An alanine scan of the NbVIM_38 paratope showed that its binding was driven by hydrophobic amino acids. The inhibitory concentration was in the µM range for all tested β-lactams. In addition, the inhibition was found to follow a mixed hyperbolic profile with a predominantly uncompetitive component. Moreover, substrate inhibition was recorded only after nanobody binding. These kinetic data are indicative of a binding site that is distant from the active site. This finding was confirmed by epitope mapping analysis that was performed using peptides, and which identified two stretches of amino acids in the L6 loop and at the end of the alpha2 helix. Because this binding site is distant from the active site and alters both the substrate binding and catalytic properties of VIM-4, this nanobody can be considered as an allosteric inhibitor. [less ▲]

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See detailCA1838, A NANOBODY INHIBITING THE METALLO-β-LACTAMASE VIM-4.
Sohier, Jean ULg; Laurent, Clémentine ULg; Pardon, Els et al

Poster (2010)

Detailed reference viewed: 17 (16 ULg)
See detailcAbVIM4, a nanobody inhibiting the metallo-β-lactamase VIM-4
Sohier, Jean ULg; Laurent, Clémentine ULg; Pardon, Els et al

Poster (2010)

Detailed reference viewed: 11 (9 ULg)
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See detailCharacterisation of B1 metallo-beta-lactamase inhibition by VHHs
Sohier, Jean ULg; Laurent, Clémentine ULg; Chevigné, Andy et al

Poster (2010)

Detailed reference viewed: 38 (16 ULg)