Amino acid:[carrier protein] ligases – homologs of seryl-tRNA synthetases

Numerous examples of aaRS-like proteins that function outside ribosomal translation have been described in recent years. Examples include PoxA, an enzyme catalyzing posttranslational modification of elongation factor P (EF-P), AsnA reassigned to asparagine biosynthesis, MshC devoted to biosynthesis of mycothiol, a thiol protecting actinomycetes from oxidative stress and electrophilic toxins, catalytically inactive SLIMP indispensable for proper mitochondrial function and biogenesis in insects, cyclodipeptide synthetases, etc.

The focus of our research are amino acid:[carrier protein] ligases (aa:CP ligases), enzymes homologous to atypical SerRS. Aa:CP ligases are widespread in several bacterial genera, and catalyze aminoacylation of particular carrier proteins. Although they are structurally remarkably similar to seryl-tRNA synthetases, they use other amino acids, namely glycine or alanine, to charge dedicated carrier proteins, instead of tRNA. Structural, biochemical and computational studies conducted in our group and by our collaborators revealed many mechanistic and structural details how the catalytic core of SerRS was redesigned to interact with carrier proteins instead of tRNA, and how the amino acid specificity has changed.

The biological role of these remarkable SerRS homologs is unknown, and it is the subject of our current investigations. We are interested in evolutionary relations between aaRS and aa:CP ligases, their taxonomic distribution, and we are exploring amino acid specificity of diverse members of this novel enzyme family.