Crystal structures that suggest late development of genetic code components for differentiating aromatic side chains
| Autor: | Francella J. Otero, Xiang-Lei Yang, Paul Schimmel, Duncan E. McRee, Robert J. Skene, Lluís Ribas de Pouplana |
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| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Models
Molecular Protein Conformation Molecular Sequence Data Sequence alignment Tryptophan-tRNA Ligase Biology Crystallography X-Ray Sensitivity and Specificity Geobacillus stearothermophilus chemistry.chemical_compound Protein structure Aromatic amino acids Humans Amino Acid Sequence Tyrosine Peptide sequence Conserved Sequence Phylogeny chemistry.chemical_classification Multidisciplinary Binding Sites Sequence Homology Amino Acid Tryptophan Biological Sciences Genetic code Adenosine Monophosphate Amino acid chemistry Biochemistry Genetic Code Sequence Alignment |
| Popis: | Early forms of the genetic code likely generated “statistical” proteins, with similar side chains occupying the same sequence positions at different ratios. In this scenario, groups of related side chains were treated by aminoacyl-tRNA synthetases as a single molecular species until a discrimination mechanism developed that could separate them. The aromatic amino acids tryptophan, tyrosine, and phenylalanine likely constituted one of these groups. A crystal structure of human tryptophanyl-tRNA synthetase was solved at 2.1 Å with a tryptophanyl-adenylate bound at the active site. A cocrystal structure of an active fragment of human tyrosyl-tRNA synthetase with its cognate amino acid analog was also solved at 1.6 Å. The two structures enabled active site identifications and provided the information for structure-based sequence alignments of ≈45 orthologs of each enzyme. Two critical positions shared by all tyrosyl-tRNA synthetases and tryptophanyl-tRNA synthetases for amino acid discrimination were identified. The variations at these two positions and phylogenetic analyses based on the structural information suggest that, in contrast to many other amino acids, discrimination of tyrosine from tryptophan occurred late in the development of the genetic code. |
| Databáze: | OpenAIRE |
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