Evolution of a family of metazoan active-site-serine enzymes from penicillin-binding proteins: a novel facet of the bacterial legacy

Abstract

BACKGROUND: Bacterial penicillin-binding proteins and beta-lactamases (PBP-betaLs) constitute a large family of serine proteases that perform essential functions in the synthesis and maintenance of peptidoglycan. Intriguingly, genes encoding PBP-betaL homologs occur in many metazoan genomes including humans. The emerging role of LACTB, a mammalian mitochondrial PBP-betaL homolog, in metabolic signaling prompted us to investigate the evolutionary history of metazoan PBP-betaL proteins. RESULTS: Metazoan PBP-betaL homologs including LACTB share unique structural features with bacterial class B low molecular weight penicillin-binding proteins. The amino acid residues necessary for enzymatic activity in bacterial PBP-betaL proteins, including the catalytic serine residue, are conserved in all metazoan homologs. Phylogenetic analysis indicated that metazoan PBP-betaL homologs comprise four alloparalogus protein lineages that derive from alpha-proteobacteria. CONCLUSION: While most components of the peptidoglycan synthesis machinery were dumped by early eukaryotes, a few PBP-betaL proteins were conserved and are found in metazoans including humans. Metazoan PBP-betaL homologs are active-site-serine enzymes that probably have distinct functions in the metabolic circuitry. We hypothesize that PBP-betaL proteins in the early eukaryotic cell enabled the degradation of peptidoglycan from ingested bacteria, thereby maximizing the yield of nutrients and streamlining the cell for effective phagocytotic feeding.