Research article

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

Nina Peitsaro^1,2 , Zydrune Polianskyte^1,2 , Jarno Tuimala³ , Isabella Pörn-Ares^1,2 , Julius Liobikas² , Oliver Speer² , Dan Lindholm⁴ , James Thompson⁵ and Ove Eriksson^1,2

¹Research Program of Molecular Neurology, Biomedicum Helsinki, P.O. Box 63, FIN-00014 University of Helsinki, Finland

²Helsinki Biophysics and Biomembrane Group, Institute of Biomedicine, P.O. Box 63, FIN-00014 University of Helsinki, Finland

³CSC-Scientific Computing Ltd, P.O. Box 405, FIN-02101 Espoo, Finland

⁴Minerva Medical Research Institute, Biomedicum Helsinki, FIN-00290 Helsinki, Finland

⁵Androgen Receptor Laboratory, Institute of Biomedicine, P.O. Box 63, FIN-00014 University of Helsinki, Finland

author email corresponding author email

BMC Evolutionary Biology 2008, 8:26doi:10.1186/1471-2148-8-26

Published:	28 January 2008

Abstract

Background

Bacterial penicillin-binding proteins and β-lactamases (PBP-βLs) constitute a large family of serine proteases that perform essential functions in the synthesis and maintenance of peptidoglycan. Intriguingly, genes encoding PBP-βL homologs occur in many metazoan genomes including humans. The emerging role of LACTB, a mammalian mitochondrial PBP-βL homolog, in metabolic signaling prompted us to investigate the evolutionary history of metazoan PBP-βL proteins.

Results

Metazoan PBP-βL 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-βL proteins, including the catalytic serine residue, are conserved in all metazoan homologs. Phylogenetic analysis indicated that metazoan PBP-βL homologs comprise four alloparalogus protein lineages that derive from α-proteobacteria.

Conclusion

While most components of the peptidoglycan synthesis machinery were dumped by early eukaryotes, a few PBP-βL proteins were conserved and are found in metazoans including humans. Metazoan PBP-βL homologs are active-site-serine enzymes that probably have distinct functions in the metabolic circuitry. We hypothesize that PBP-βL 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.