PDBsum entry 1r6t

Ligase

PDB id: 1r6t

Contents

Protein chains

440 a.a. *

362 a.a. *

Ligands

TYM

GOL ×2

Waters ×294

* Residue conservation analysis

References listed in PDB file

Key reference

Title

Crystal structures that suggest late development of genetic code components for differentiating aromatic side chains.

Authors

X.L.Yang, F.J.Otero, R.J.Skene, D.E.Mcree, P.Schimmel, L.Ribas de pouplana.

Ref.

Proc Natl Acad Sci U S A, 2003, 100, 15376-15380. [DOI no: 10.1073/pnas.2136794100]

PubMed id

14671330

Abstract

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 A 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 A. The two structures enabled active site identifications and provided the information for structure-based sequence alignments of approximately 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.

Figure 1.
Fig. 1. Classification of aminoacyl-tRNA synthetases adapted from ref. 5. The 20 synthetases are divided into 2 classes of 10 enzymes each. The exceptional class I LysRS is shown in gray. Highlighted with a yellow box, TyrRS and TrpRS from class Ic are paired with PheRS from class IIc.

Figure 2.
Fig. 2. Structure of the dimeric human TrpRS with one monomer shown in color. The circled CP1 insertion of the Rossmann fold domain forms the dimerization interface. All three domains [N-terminal appended domain (blue), Rossmann fold catalytic domain (yellow), and anticodon recognition domain (green)] were resolved in one monomer of the dimer with a disordered linker of 21 residues connecting the N-domain and the Rossmann fold domain. However, in the other monomer, the first 96 residues, which include the N-terminal domain, the linker region, and part of the Rossmann fold catalytic domain, were completely disordered. A bound Trp-AMP was found only in the monomer with the resolved N-domain.