Six Rossmannoid folds, including the Class I aminoacyl-tRNA synthetases, share a partial core with the anti-codon-binding domain of a Class II aminoacyl-tRNA synthetase

Abstract

cammer@vbi.vt.edu.

Functional Class I and II Amino Acid-activating Enzymes Can Be Coded by Opposite Strands of the Same Gene

“…The corner between what in full-length crystal structures is the ␣-helix and the second ␤-strand of the Class I 46-mer occurs with minimal variation of amino acid, spacing, and three-dimensional packing in ϳ125 different protein families from the Rossmannoid superfamily (44), the largest in the proteome (47)(48)(49). P-loop peptides studied by also arguably have structural homology to parts of the Class I aaRS 46-mers that bind ATP; the segment N-terminal to the first helix shares glycines in homologous positions before, within, and following the Class I HIGH signature.…”

Full Implementation of the Genetic Code by Tryptophanyl-tRNA Synthetase Requires Intermodular Coupling

“…This 46-residue module also contains important switching residues (Ile-4, Phe-26, Tyr-33, and Phe-37) that are involved in allosteric behavior (15). The central importance of NTP utilization in biology suggests that these factors may account for the fact that this module is arguably the most highly conserved packing motif in the proteome (31).…”

“…Our previous work (15,31) identified a key component of allosteric behavior in the D1 switch that is contained entirely within the Urzyme. That switching mechanism could have been sensitive to the presence of other modules in trans.…”

“…That they may have existed seems reasonable in light of the idiosyncrasy and multiple usage of the ␣-helix bundles (most Class I aaR), oligonucleotide binding folds in Class IIB aaRS (35), and Rossmannoid domains Class IIA (29,31) as ABDs. Thus, it seems more likely that the Urzyme accumulated the rudimentary CP1 domain present in TrpRS in a single event, possibly via a transposable element that eventually invaded all Class I Urzymes and whose selective advantage may have been to enhance amino acid specificity when potentiated by stand-alone ABDs.…”

Enhanced Amino Acid Selection in Fully Evolved Tryptophanyl-tRNA Synthetase, Relative to Its Urzyme, Requires Domain Motion Sensed by the D1 Switch, a Remote Dynamic Packing Motif

“…Instead, we identified a long range allosteric influence (5) from a widely distributed and highly conserved core-packing motif (6) remote from the active site that accounted entirely for the catalytic assist by Mg 2ϩ . This motif is the most extensive of four discrete locations where Delaunay tessellation patterns change during TrpRS catalysis, suggesting the name "D1 Switch" (7).…”