1D2R

2.9 A CRYSTAL STRUCTURE OF LIGAND-FREE TRYPTOPHANYL-TRNA SYNTHETASE: DOMAIN MOVEMENTS FRAGMENT THE ADENINE NUCLEOTIDE BINDING SITE.

Summary for 1D2R

• Entry DOI: 10.2210/pdb1d2r/pdb
• Descriptor: PROTEIN (TRYPTOPHANYL TRNA SYNTHETASE) (1 entity in total)
• Functional Keywords: class i trna synthetase, aars, induced fit, trprs, ligase
• Biological source: Geobacillus stearothermophilus
• Cellular location: Cytoplasm : P00953
• Total number of polymer chains: 6
• Total formula weight: 220506.54

Authors

Ilyin, V.A.,Carter Jr., C.W. (deposition date: 1999-09-27, release date: 2000-04-05, Last modification date: 2024-02-07)

Primary citation

Ilyin, V.A.,Temple, B.,Hu, M.,Li, G.,Yin, Y.,Vachette, P.,Carter Jr., C.W.
2.9 A crystal structure of ligand-free tryptophanyl-tRNA synthetase: domain movements fragment the adenine nucleotide binding site.
Protein Sci., 9:218-231, 2000

PubMed Abstract: The crystal structure of ligand-free tryptophanyl-tRNA synthetase (TrpRS) was solved at 2.9 A using a combination of molecular replacement and maximum-entropy map/phase improvement. The dimeric structure (R = 23.7, Rfree = 26.2) is asymmetric, unlike that of the TrpRS tryptophanyl-5'AMP complex (TAM; Doublié S, Bricogne G, Gilmore CJ, Carter CW Jr, 1995, Structure 3:17-31). In agreement with small-angle solution X-ray scattering experiments, unliganded TrpRS has a conformation in which both monomers open, leaving only the tryptophan-binding regions of their active sites intact. The amino terminal alphaA-helix, TIGN, and KMSKS signature sequences, and the distal helical domain rotate as a single rigid body away from the dinucleotide-binding fold domain, opening the AMP binding site, seen in the TAM complex, into two halves. Comparison of side-chain packing in ligand-free TrpRS and the TAM complex, using identification of nonpolar nuclei (Ilyin VA, 1994, Protein Eng 7:1189-1195), shows that significant repacking occurs between three relatively stable core regions, one of which acts as a bearing between the other two. These domain rearrangements provide a new structural paradigm that is consistent in detail with the "induced-fit" mechanism proposed for TyrRS by Fersht et al. (Fersht AR, Knill-Jones JW, Beduelle H, Winter G, 1988, Biochemistry 27:1581-1587). Coupling of ATP binding determinants associated with the two catalytic signature sequences to the helical domain containing the presumptive anticodon-binding site provides a mechanism to coordinate active-site chemistry with relocation of the major tRNA binding determinants.

PubMed: 10716174

Experimental method

X-RAY DIFFRACTION (2.9 Å)