title: A minimal TrpRS catalytic domain supports sense/antisense ancestry of class I and II aminoacyl-tRNA synthetases.
abstract: The emergence of polypeptide catalysts for amino acid activation, the slowest step in protein synthesis, poses a significant puzzle associated with the origin of biology. This problem is compounded as the 20 contemporary aminoacyl-tRNA synthetases belong to two quite distinct families. We describe here the use of protein design to show experimentally that a minimal class I aminoacyl-tRNA synthetase active site might have functioned in the distant past. We deleted the anticodon binding domain from tryptophanyl-tRNA synthetase and fused the discontinuous segments comprising its active site. The resulting 130 residue minimal catalytic domain activates tryptophan. This residual catalytic activity constitutes the first experimental evidence that the conserved class I signature sequences, HIGH and KMSKS, might have arisen in-frame, opposite motifs 2 and 1 from class II, as complementary sense and antisense strands of the same ancestral gene.
authors: Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors: Yen
authors: Y
authors: Pham
authors: Li
authors: L
authors: Li
authors: Aram
authors: A
authors: Kim
authors: Ozgun
authors: O
authors: Erdogan
authors: Violetta
authors: V
authors: Weinreb
authors: Glenn L
authors: GL
authors: Butterfoss
authors: Brian
authors: B
authors: Kuhlman
authors: Charles W
authors: CW
authors: Carter
mesh_terms: D000604:Amino Acyl-tRNA Synthetases / Q000737:chemistry / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D016375:Antisense Elements (Genetics); D001665:Binding Sites; D020134:Catalytic Domain; D017124:Conserved Sequence; D019143:Evolution, Molecular; D007700:Kinetics; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D014364:Tryptophan / Q000378:metabolism
chemical_list: D016375:Antisense Elements (Genetics); D014364:Tryptophan; D000604:Amino Acyl-tRNA Synthetases