InterPro domain: IPR001466

This entry represents the serine beta-lactamase-like superfamily. It is a group of diverse group of sequences that includes D-alanyl-D-alanine carboxypeptidase B, aminopeptidase (DmpB), alkaline D-peptidase, animal D-Ala-D-Ala carboxypeptidase homologues and the class A and C beta-lactamases and eukaryotic beta-lactamase homologues which are variously described as: transesterases, non-ribosomal peptide synthetases and hypothetical proteins. Many are serine peptidases belonging to MEROPS peptidase families S11 (D-Ala-D-Ala carboxypeptidase A family) and S12 (D-Ala-D-Ala carboxypeptidase B family, clan SE). The beta-lactamases are classified as both S11 and S12 non-peptidase homologues; these either have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for the catalytic activity.

Beta-lactamase catalyses the opening and hydrolysis of the beta-lactam ring of beta-lactam antibiotics such as penicillins and cephalosporins [ 1 ]. 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 [ 2 ]. 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 - 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.

1. Beta-lactamase of Bacillus licheniformis 749/C. Refinement at 2 A resolution and analysis of hydration. J. Mol. Biol. 220, 435-55
2. The phototrophic bacterium Rhodopseudomonas capsulata sp108 encodes an indigenous class A beta-lactamase. Biochem. J. 260, 803-12
3. The active-site-serine penicillin-recognizing enzymes as members of the Streptomyces R61 DD-peptidase family. Biochem. J. 250, 313-24