8 research outputs found
Inhibition by L-aspartol adenylate of a nondiscriminating aspartyl-tRNA synthetase reveals differences between the interactions of its active site with tRNA Asp
Structure of the unusual seryl-tRNA synthetase reveals a distinct zinc-dependent mode of substrate recognition
Methanogenic archaea possess unusual seryl-tRNA synthetase (SerRS), evolutionarily distinct from the SerRSs found in other archaea, eucaryotes and bacteria. The two types of SerRSs show only minimal sequence similarity, primarily within class II conserved motifs 1, 2 and 3. Here, we report a 2.5 Ă
resolution crystal structure of the atypical methanogenic Methanosarcina barkeri SerRS and its complexes with ATP, serine and the nonhydrolysable seryl-adenylate analogue 5âČ-O-(N-serylsulfamoyl)adenosine. The structures reveal two idiosyncratic features of methanogenic SerRSs: a novel N-terminal tRNA-binding domain and an active site zinc ion. The tetra-coordinated Zn(2+) ion is bound to three conserved protein ligands (Cys306, Glu355 and Cys461) and binds the amino group of the serine substrate. The absolute requirement of the metal ion for enzymatic activity was confirmed by mutational analysis of the direct zinc ion ligands. This zinc-dependent serine recognition mechanism differs fundamentally from the one employed by the bacterial-type SerRSs. Consequently, SerRS represents the only known aminoacyl-tRNA synthetase system that evolved two distinct mechanisms for the recognition of the same amino-acid substrate
The DUSPâUbl domain of USP4 enhances its catalytic efficiency by promoting ubiquitin exchange
Fusion with Anticodon Binding Domain of GluRS is Not Sufficient to Alter the Substrate Specificity of a Chimeric Glu-Q-RS
Emergence and Evolution
The aminoacyl-tRNA synthetases (aaRSs) are essential components of the protein synthesis machinery responsible for defining the genetic code by pairing the correct amino acids to their cognate tRNAs. The aaRSs are an ancient enzyme family believed to have origins that may predate the last common ancestor and as such they provide insights into the evolution and development of the extant genetic code. Although the aaRSs have long been viewed as a highly conserved group of enzymes, findings within the last couple of decades have started to demonstrate how diverse and versatile these enzymes really are. Beyond their central role in translation, aaRSs and their numerous homologs have evolved a wide array of alternative functions both inside and outside translation. Current understanding of the emergence of the aaRSs, and their subsequent evolution into a functionally diverse enzyme family, are discussed in this chapter