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Overview for MACiE Entry M0309

Version history

General Information

EC Number: 6.1.1.5 (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:

  • 3.40.50.620 - Tyrosyl-Transfer RNA Synthetase , subunit E, domain 1

"Other" CATH Codes:

Display structure information

Overall Reaction:

Image of L-Isoleucine

Image of ATP

Image of tRNA (Isoleucine)

right arrow

Image of Isoleucyl-tRNA

Image of AMP

Image of diphosphate

L-Isoleucine
C00407
CHEBI:17191
ATP
C00002
CHEBI:15422
tRNA (Isoleucine)
C01644
CHEBI:29174
Isoleucyl-tRNA
C03127
CHEBI:29160
AMP
C00020
CHEBI:16027
diphosphate
C00013
CHEBI:45212

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 1The zwitterionic leucine substrate attacks the alpha phosphate of ATP, forming an activated, adenylated, amino acid.
Step 2The 2' end of the specific tRNA molecule attacks at the activated phospho-ester bond.
Step 3The anionic, tetrahedral intermediate collapses, generating the tRNA-isoleucine adduct and AMP.

View similar reactions (composite manual annotation)


Catalytic Residues Involved

Type Number Chain Location of Function
Lys 591 A Side Chain
Lys 594 A Side Chain
Pro 46 A Side Chain
Trp 518 A Side Chain
Trp 558 A Side Chain
Asp 85 A Side Chain
Gln 554 A Side Chain

Metal Cofactors for M0309

Type Het group Number Chain
zinc ZN 1101 A Overview
zinc ZN 1102 A Overview
magnesium No Available PDB Information

References

  1. O. Nureki et al. (1998), Science, 280, 578-582. Enzyme structure with two catalytic sites for double-sieve selection of substrate.
    Medline: 9554847
  2. S. Fukai et al. (2003), RNA, 9, 100-111. Mechanism of molecular interactions for tRNA(Val) recognition by valyl-tRNA synthetase.
    Medline: 12554880
  3. A. R. Fersht (1977), Biochemistry, 16, 1025-1030. Editing mechanisms in protein synthesis. Rejection of valine by the isoleucyl-tRNA synthetase.
    Medline: 321008
  4. M. Ibba et al. (2000), Annu. Rev. Biochem., 69, 617-150. Aminoacyl-tRNA synthesis.
    Medline: 10966471

Homologue information for M0309 (1ile)

CSA Homologues

MACiE Homologues (within the PDB)

MACiE Homologues (within UniprotKB/SwissProt)



Entries with at least one Catalytic CATH code in common (different mechanisms):

MACiE Entry Enzyme Name
EC Number
PDB code CATH code Composite
Reaction Similarity
Catalytic Machinery
Similarity
M0279 phosphoadenylyl-sulfate reductase (thioredoxin)
1.8.4.8
1sur 3.40.50.620
0.05550.1894Compare
M0299 pantetheine-phosphate adenylyltransferase
2.7.7.3
1b6t 3.40.50.620
0.250.1506Compare
M0287 sulfate adenylyltransferase
2.7.7.4
1g8f 3.40.50.620
0.30760Compare
M0296 glycerol-3-phosphate cytidylyltransferase
2.7.7.39
1n1d 3.40.50.620
0.250.3358Compare
M0197 tyrosine-tRNA ligase
6.1.1.1
2ts1 3.40.50.620
0.750.3234Compare
M0235 arginine-tRNA ligase
6.1.1.19
1f7u 3.40.50.620
1.10.730.10
0.83330.1285Compare
M0229 pantoate-beta-alanine ligase
6.3.2.1
2a84 3.40.50.620
0.50.0138Compare
M0303 (carboxyethyl)arginine beta-lactam-synthase
6.3.3.4
1mb9 3.40.50.620
0.36840.1499Compare
M0316 argininosuccinate synthetase
6.3.4.5
1j21 3.40.50.620
0.3750Compare
M0234 GMP synthase (glutamine-hydrolysing)
6.3.5.2
1gpm 3.40.50.620
0.2820.1919Compare
M0302 asparagine synthase (glutamine-hydrolysing)
6.3.5.4
1ct9 3.40.50.620
0.24240.0089Compare

View a comparison of the other reactions in MACiE with the CATH domain 3.40.50.620


Links to this entry in other databases

Link to EC-PDB-SUM Link to PDB-SUM Link to RCSB PDB Link to PDBe Link to CSA
Link to MetaCyc Link to KEGG Link to BRENDA Link to ExplorENZ
Link to EzCatDB

GOA logo
nucleotide binding (molecular function)
aminoacyl-tRNA ligase activity (molecular function)
isoleucine-tRNA ligase activity (molecular function)
ATP binding (molecular function)
cytoplasm (cellular component)
translation (biological process)
tRNA aminoacylation for protein translation (biological process)
isoleucyl-tRNA aminoacylation (biological process)
zinc ion binding (molecular function)
ligase activity (molecular function)
metal ion binding (molecular function)
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