PT  - JOURNAL ARTICLE
AU  - Florian Kaiser
AU  - Sebastian Bittrich
AU  - Sebastian Salentin
AU  - Christoph Leberecht
AU  - V. Joachim Haupt
AU  - Sarah Krautwurst
AU  - Michael Schroeder
AU  - Dirk Labudde
TI  - Backbone brackets and arginine tweezers delineate class I and class II aminoacyl tRNA synthetases
AID  - 10.1101/198846
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 198846
4099  - http://biorxiv.org/content/early/2017/10/09/198846.short
4100  - http://biorxiv.org/content/early/2017/10/09/198846.full
AB  - All living organisms share the machinery to translate RNA into amino acid sequences. One key component of this machinery are aminoacyl tRNA synthetases, which ligate tRNAs to amino acids. Sequence analyses revealed that these enzymes evolved to complementary classes, which can be characterized by several sequence motifs. However, there are no structural motifs, which capture the core function of the classes: high specificity ligand interaction. We identified backbone brackets and arginine tweezers and show that these two motifs optimize ligand recognition with complementary mechanisms. They are the most compact and simple characteristic to distinguish the aminoacyl tRNA synthetase class I from II. These findings support the hypothesis that the evolutionary convergence regarding function of aminoacyl tRNA synthetases was balanced by a divergence regarding ligand interaction.Author summary Aminoacyl tRNA synthetases (aaRS) are primordial enzymes essential for interpretation and transfer of genetic information. Disturbances in this fine-tuned system lead to severe malfunctions in organisms and to lethal diseases. The increasing amount of experimentally determined three-dimensional structures of aaRS opens up new avenues for high-throughput analyses of molecular mechanisms. In this study, we present an exhaustive structural analysis of the binding mechanisms of aaRS enzymes and discuss ligand recognition motifs. We unveil a divergent implementation of enzyme substrate recognition in each aaRS class. While class I binds via interactions mediated by conserved backbone hydrogen bonds, class II uses a pair of arginine residues to establish salt bridges. We show how evolution achieves binding of the same ligand species with completely different mechanisms. In addition, we demonstrate that sequence analysis for conserved residues may miss important functional aspects which can only be revealed by structural studies. Further detailed insights in aaRS substrate interaction and a manually curated high-quality dataset of aaRS structures serve as a rich resource for in-depth studies of these extraordinary enzymes.