title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Research Program of Molecular Neurology, Biomedicum Helsinki, P.O. Box 63, FIN-00014 University of Helsinki, Finland. Nina.Peitsaro@helsinki.fi
authors.forename: Nina
authors.initials: N
authors.lastname: Peitsaro
authors.forename: Zydrune
authors.initials: Z
authors.lastname: Polianskyte
authors.forename: Jarno
authors.initials: J
authors.lastname: Tuimala
authors.forename: Isabella
authors.initials: I
authors.lastname: Pörn-Ares
authors.forename: Julius
authors.initials: J
authors.lastname: Liobikas
authors.forename: Oliver
authors.initials: O
authors.lastname: Speer
authors.forename: Dan
authors.initials: D
authors.lastname: Lindholm
authors.forename: James
authors.initials: J
authors.lastname: Thompson
authors.forename: Ove
authors.initials: O
authors.lastname: Eriksson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D017124:Conserved Sequence; D019143:Evolution, Molecular; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D024101:Mitochondrial Proteins; D008970:Molecular Weight; D046915:Penicillin-Binding Proteins / Q000378:metabolism*; D012269:Ribosomal Proteins / Q000235:genetics; D016415:Sequence Alignment; D017385:Sequence Homology; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D046915:Penicillin-Binding Proteins; D012269:Ribosomal Proteins; C486706:LACTB protein, human; D001618:beta-Lactamases