InterPro: IPR000871 Beta-lactamase, class A/D

Beta-lactamase catalyses the opening and hydrolysis of the beta-lactam ring of beta-lactam antibiotics such as penicillins and cephalosporins. There are four groups, classed A, B, C and D according to sequence, substrate specificity, and kinetic behaviour. Class A (penicillinase-type) is the most common [1]. The genes for class A beta-lactamases are widely distributed in bacteria, frequently located on transmissible plasmids in Gram-negative organisms, although an equivalent chromosomal gene has been found in a few species [2]. Class A, C and D beta-lactamases are serine-utilising hydrolases, while class B enzymes utilise a catalytic zinc centre instead. The 3 classes of serine beta-lactamase are evolutionarily related and belong to a superfamily that also includes DD-peptidases and other penicillin-binding proteins [3]. All these proteins contain an S-x-x-K motif, the Ser being the active site residue. Although clearly related, however, the sequences of the 3 classes of serine beta-lactamases vary considerably outside the active site.

This entry represents the Group 2 beta-lactamases, which correspond to the penicillinases and cephalosporinases, which are inhibited by clavulanic acid. They corresponding to the molecular classes A and D reflecting the original TEM and SHV genes. However, because of the increasing number of TEM and SHV derived {beta} lactamases, they have been divided into two subclasses, 2a and 2b:

• The 2a subgroup contains just penicillinases.
• The 2b subgroup contains broad spectrum {beta} lactamases, meaning that they are capable of inactivating penicillins and cephalosporins at the same rate. Furthermore, new subgroups were segregated from subgroup 2b based on their activity against certain antibiotics and resistance to clavulanic acid.
• Molecular Class D or A Subgroup 2d enzymes inactivate cloxacillin more than benzylpenicillin, with some activity against carbenicillin; these enzymes are poorly inhibited by clavulanic acid, and some of them are extended spectrum beta-lactamases (ESBLs).

The class A and D beta-lactamases belong to MEROPS peptidase family S11 (D-Ala-D-Ala carboxypeptidase A family, clan SE).