A structure-based multiple sequence alignment of all class I aminoacyl-tRNA synthetases

Area of Science:

• Biochemistry
• Molecular Biology
• Structural Biology

Background:

• Class I aminoacyl-tRNA synthetases (aaRS) are essential enzymes involved in protein synthesis.
• The dinucleotide fold domain is conserved across various aaRS, suggesting shared structural and functional characteristics.

Purpose of the Study:

• To identify structurally equivalent amino acids within the conserved dinucleotide fold domains of MetRS, GlnRS, and TyrRS.
• To use these conserved residues to constrain sequence alignments for 10 class I aaRS.
• To predict the location and function of critical residues in other synthetases.

Main Methods:

• Comparative analysis of superimposable dinucleotide fold domains from MetRS, GlnRS, and TyrRS.
• Sequence alignment of 10 class I aminoacyl-tRNA synthetases (aaRS).
• Identification and functional prediction of conserved residues.

Main Results:

• Structurally equivalent amino acids were defined, enabling constrained sequence alignments for class I aaRS.
• Key conserved residues were identified: a negatively-charged residue for alpha-amino group binding, residues in the inserted domain, and residues for amino acid/ATP binding.
• Class I synthetases were partitioned into two subgroups: (a) MetRS, IleRS, LeuRS, ValRS, CysRS, ArgRS and (b) GlnRS, GluRS, TyrRS, TrpRS.

Conclusions:

• The conserved residues within the dinucleotide fold are critical for the catalytic activity of class I aaRS.
• Sequence alignments constrained by structural data reveal evolutionary relationships and allow functional predictions across the aaRS family.
• The identified subgroups suggest potential functional or regulatory divergence within class I aaRS.