Structure-Based Phylogenies of the Serine β-Lactamases

The serine β-lactamases present a special problem for phylogenetics because they have diverged so much that they fall into three classes that share no detectable sequence homology among themselves. Here we offer a solution to the problem in the form of two phylogenies that are based on a protein structure alignment. In the first, structural alignments were used as a guide for aligning amino acid sequences and in the second, the average root mean square distances between the alpha carbons of the proteins were used to create a pairwise distance matrix from which a neighbor-joining phylogeny was created. From those phylogenies, we show that the Class A and Class D β-lactamases are sister taxa and that the divergence of the Class C β-lactamases predated the divergence of the Class A and Class D β-lactamases.