An idiosyncratic serine ordering loop in methanogen seryl-tRNA synthetases guides substrates through seryl-tRNASer formation

► Methanogenic-type SerRS has a highly flexible motif (SOL) within the active site. ► Notable structural rearrangements of the SOL peptide parallel Ser-tRNASer formation. ► SOL may play the role in mediation of open vs closed active site conformation. ► Coupling of the SOL conformational change with active site assembly occurs via Trp396. ► His250, a non-SOL residue, is essential for transfer of serine to tRNA.