7PA5

Complex between the beta-lactamase CMY-2 with an inhibitory nanobody

Summary for 7PA5

• Entry DOI: 10.2210/pdb7pa5/pdb
• Descriptor: Beta-lactamase, nanobody, GLYCEROL, ... (5 entities in total)
• Functional Keywords: single domain camelid antibody cephalosporinase, hydrolase
• Biological source: Escherichia coli; More
• Total number of polymer chains: 2
• Total formula weight: 54291.15

Authors

Frederic Cawez, F.C.,Frederic Kerff, F.K.,Moreno Galleni, M.G.,Raphael Herman, R.H. (deposition date: 2021-07-29, release date: 2022-11-16, Last modification date: 2024-11-06)

Primary citation

Cawez, F.,Mercuri, P.S.,Morales-Yanez, F.J.,Maalouf, R.,Vandevenne, M.,Kerff, F.,Guerin, V.,Mainil, J.,Thiry, D.,Saulmont, M.,Vanderplasschen, A.,Lafaye, P.,Ayme, G.,Bogaerts, P.,Dumoulin, M.,Galleni, M.
Development of Nanobodies as Theranostic Agents against CMY-2-Like Class C beta-Lactamases.
Antimicrob.Agents Chemother., 67:e0149922-e0149922, 2023

PubMed Abstract: Three soluble single-domain fragments derived from the unique variable region of camelid heavy-chain antibodies (VHHs) against the CMY-2 β-lactamase behaved as inhibitors. The structure of the complex VHH cAb(254)/CMY-2 showed that the epitope is close to the active site and that the CDR3 of the VHH protrudes into the catalytic site. The β-lactamase inhibition pattern followed a mixed profile with a predominant noncompetitive component. The three isolated VHHs recognized overlapping epitopes since they behaved as competitive binders. Our study identified a binding site that can be targeted by a new class of β-lactamase inhibitors designed on the sequence of the paratope. Furthermore, the use of mono- or bivalent VHH and rabbit polyclonal anti-CMY-2 antibodies enables the development of the first generation of enzyme-linked immunosorbent assay (ELISA) for the detection of CMY-2 produced by CMY-2-expressing bacteria, irrespective of resistotype.

PubMed: 36892280
DOI: 10.1128/aac.01499-22

Experimental method

X-RAY DIFFRACTION (3.184 Å)