Overview for MACiE Entry M0309
EC Number: 22.214.171.124 (A member of the Ligases, Forming carbon-oxygen bonds, Ligases forming aminoacyl-tRNA and related compounds)
Enzyme Name: isoleucine-tRNA ligase
Biological Species: Thermus thermophilus (Bacteria)
Catalytic Chain UniprotKB Accession Codes:
- P56690 - Isoleucyl-tRNA synthetase
Representative PDB Code: 1ile - ISOLEUCYL-TRNA SYNTHETASE (Resolution = 2.50 Å).
Catalytic CATH Codes:
- 126.96.36.1990 - Tyrosyl-Transfer RNA Synthetase , subunit E, domain 1
"Other" CATH Codes:
Display structure information
Overall Comment: The enzyme, isoleucine-transfer RNA synthetase activates not only the cognate substrate L-isoleucine but also the structurally similar L-valine in the first, amino-acylation step. In a second, "editing" step, the synthetase itself rapidly hydrolyses only the valylated products. For this two-step substrate selection, a "double-sieve" mechanism has been proposed to explain the high substrate fidelity and low copy error of the tRNA synthetase.
View similar reactions
Stepwise Description of the Reaction
|Step 1||The zwitterionic leucine substrate attacks the alpha phosphate of ATP, forming an activated, adenylated, amino acid.|
|Step 2||The 2' end of the specific tRNA molecule attacks at the activated phospho-ester bond.|
|Step 3||The anionic, tetrahedral intermediate collapses, generating the tRNA-isoleucine adduct and AMP.|
View similar reactions (composite manual annotation)
Catalytic Residues Involved
||Location of Function
Metal Cofactors for M0309
||No Available PDB Information
- O. Nureki et al. (1998), Science, 280, 578-582. Enzyme structure with two catalytic sites for double-sieve selection of substrate.
- S. Fukai et al. (2003), RNA, 9, 100-111. Mechanism of molecular interactions for tRNA(Val) recognition by valyl-tRNA synthetase.
- A. R. Fersht (1977), Biochemistry, 16, 1025-1030. Editing mechanisms in protein synthesis. Rejection of valine by the isoleucyl-tRNA synthetase.
- M. Ibba et al. (2000), Annu. Rev. Biochem., 69, 617-150. Aminoacyl-tRNA synthesis.
Homologue information for M0309 (1ile)
MACiE Homologues (within the PDB)
MACiE Homologues (within UniprotKB/SwissProt)
Entries with at least one Catalytic CATH code in common (different mechanisms):
|M0279 ||phosphoadenylyl-sulfate reductase (thioredoxin) |
|M0299 ||pantetheine-phosphate adenylyltransferase |
|M0287 ||sulfate adenylyltransferase |
|M0296 ||glycerol-3-phosphate cytidylyltransferase |
|M0197 ||tyrosine-tRNA ligase |
|M0235 ||arginine-tRNA ligase |
|M0229 ||pantoate-beta-alanine ligase |
|M0303 ||(carboxyethyl)arginine beta-lactam-synthase |
|M0316 ||argininosuccinate synthetase |
|M0234 ||GMP synthase (glutamine-hydrolysing) |
|M0302 ||asparagine synthase (glutamine-hydrolysing) |
View a comparison of the other reactions in MACiE with the CATH domain 188.8.131.520
Links to this entry in other databases