Table 1. Overview of the β-lactamase enzymes investigated in this study.

Enzymes GES-1, –2 and –11 as well as KPC-2 and –3 belong to the same phylogenetic cluster (GES-42 and KPC-44, respectively, see Supplementary file 1). All other tested enzymes belong to distinct phylogenetic clusters (Supplementary file 1). The ‘Cysteine positions’ column states the positions of cysteine residues after position 30 and hence, does not include amino acids that would be part of the periplasmic signal sequence. All β-lactamase enzymes except L2-1 (shaded in grey; PDB ID: 1O7E) have one disulfide bond. The ‘Mobile’ column refers to the genetic location of the β-lactamase gene; ‘yes’ indicates that the gene of interest is located on a plasmid, while ‘no’ refers to chromosomally encoded enzymes. All tested enzymes have a broad hydrolytic spectrum and are either Extended Spectrum β-Lactamases (ESBLs) or carbapenemases. The ‘Inhibition’ column refers to classical inhibitor susceptibility that is, susceptibility to inhibition by clavulanic acid, tazobactam, or sulbactam.

Enzyme	Amblerclass	Cysteine positions	Mobile	Spectrum	Inhibition
L2-1	A	C82 C136 C233	no	ESBL	yes
GES-1	A	C63 C233	yes	ESBL	yes
GES-2	A	C63 C233	yes	ESBL	yes
GES-11	A	C63 C233	yes	Carbapenemase	yes
SHV-27	A	C73 C119	no	ESBL	yes
OXA-4	D	C43 C63	yes	ESBL	yes
OXA-10	D	C44 C51	yes	ESBL	no (Aubert et al., 2001)
OXA-198	D	C116 C119	yes	Carbapenemase	no (El Garch et al., 2011)
FRI-1	A	C68 C238	yes	Carbapenemase	no (Dortet et al., 2015)
L1-1	B3	C239 C267	no	Carbapenemase	no (Palzkill, 2013)
KPC-2	A	C68 C237	yes	Carbapenemase	no (Papp-Wallace et al., 2010)
KPC-3	A	C68 C237	yes	Carbapenemase	no (Papp-Wallace et al., 2010)
SME-1	A	C72 C242	no	Carbapenemase	yes