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Information on EC 6.1.1.5 - isoleucine-tRNA ligase and Organism(s) Staphylococcus aureus and UniProt Accession P41368

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Staphylococcus aureus
UNIPROT: P41368 not found.
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The taxonomic range for the selected organisms is: Staphylococcus aureus
The enzyme appears in selected viruses and cellular organisms
Synonyms
isoleucyl-trna synthetase, ilers, iars2, isoleucyl trna synthetase, iles2, ile-trna synthetase, isoleucine-trna synthetase, mitochondrial isoleucyl-trna synthetase, iles1, isoleucyl-transfer rna synthetase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Isoleucine translase
-
Isoleucine--tRNA ligase
-
Isoleucine-transfer RNA ligase
-
Isoleucine-tRNA synthetase
-
Isoleucyl-transfer ribonucleate synthetase
-
Isoleucyl-transfer RNA synthetase
-
Isoleucyl-tRNA synthetase
-
Mupirocin resistance protein
-
Synthetase, isoleucyl-transfer ribonucleate
-
IleRS
Isoleucine translase
Isoleucine--tRNA ligase
Isoleucine-transfer RNA ligase
Isoleucine-tRNA synthetase
isoleucyl tRNA synthetase
-
-
Isoleucyl-transfer ribonucleate synthetase
Isoleucyl-transfer RNA synthetase
Isoleucyl-tRNA synthetase
Mupirocin resistance protein
Synthetase, isoleucyl-transfer ribonucleate
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
ATP + L-isoleucine + tRNAIle = AMP + diphosphate + L-isoleucyl-tRNAIle
show the reaction diagram
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
esterification
aminacylation
deacylation
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
L-isoleucine:tRNAIle ligase (AMP-forming)
-
CAS REGISTRY NUMBER
COMMENTARY hide
9030-96-0
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + L-isoleucine + tRNAIle
AMP + diphosphate + L-isoleucyl-tRNAIle
show the reaction diagram
-
-
?
ATP + L-isoleucine + tRNAIle
AMP + diphosphate + L-isoleucyl-tRNAIle
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + L-isoleucine + tRNAIle
AMP + diphosphate + L-isoleucyl-tRNAIle
show the reaction diagram
-
-
?
ATP + L-isoleucine + tRNAIle
AMP + diphosphate + L-isoleucyl-tRNAIle
show the reaction diagram
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
7-[4-[(2S,3S)-2-amino-3-methyl-1-oxopentyl]amino]butanoyl-2,4a,5,6,7,7a-hexahydro-2-methyl-1H-cyclopenta[c]pyridine-4-carboxamide
-
derivative of SB-203207, 26% inhibition at 0.1 mM
7-[[(2S,3S)-2-amino-3-methyl-1-oxopentyl]amino]sulfonylacetyloxy-2,4a,5,6,7,7a-hexahydro-2-methyl-1H-cyclopenta[c]pyridine-4-carboxamide
-
-
7-[[(2S,3S)-2-amino-3-methyl-1-oxopentyl]amino]sulfonylacetyloxy-2,4a,5,6,7,7a-hexahydro-2-methyl-1H-cyclopenta[c]pyridine-4-carboxylic acid methyl ester
-
derivative of SB-203207, 31% inhibition at 0.1 mM
7-[[(2S,3S)-2-amino-3-methyl-1-oxopentyl]amino]sulfonylacetyloxy-4,4a,5,6,7,7a-hexahydro-1-methyl-1H-cyclopenta[b]pyridine-3-carboxylic acid methyl ester
-
derivative of SB-203207, 34% inhibition at 0.1 mM
7-[[(S)-2-amino-1-oxo-5-thiahexyl]amino]sulfonylacetyloxy-2,4a,5,6,7,7a-hexahydro-2-methyl-1H-cyclopenta[c]pyridine-4-carboxamide
-
derivative of SB-203207, 38% inhibition at 0.1 mM
7-[[(S)-2-amino-1-oxo-hexyl]amino]sulfonylacetyloxy-2,4a,5,6,7,7a-hexahydro-2-methyl-1H-cyclopenta[c]pyridine-4-carboxamide
-
derivative of SB-203207, 46% inhibition at 0.1 mM
7-[[(S)-2-amino-3-methyl-1-oxobutyl]amino]sulfonylacetyloxy-2,4a,5,6,7,7a-hexahydro-2-methyl-1H-cyclopenta[c]pyridine-4-carboxylic acid methyl ester
-
derivative of SB-203207, 38% inhibition at 0.1 mM
7-[[(S)-2-amino-3-methyl-1-oxobutyl]amino]sulfonylacetyloxy-4,4a,5,6,7,7a-hexahydro-1-methyl-1H-cyclopenta[b]pyridine-3-carboxylic acid methyl ester
-
derivative of SB-203207, 10% inhibition at 0.1 mM
7-[[(S)-2-amino-3-methyl-1-oxopentyl]amino]sulfonylacetyloxy-4,4a,5,6,7,7a-hexahydro-1-methyl-1H-cyclopenta[b]pyridine-3-carboxylic acid methyl ester
-
derivative of SB-203207, 15% inhibition at 0.1 mM
chymotrypsin
-
proteolytic inactivation patterns, bound Ile-AMP or inhibitors isoleucinol adenylate and pseudomonic acid protect, 50fold higher concentration is needed for digestion of Ile-AMP-enzyme complex than for the free enzyme at 37°C
-
ethyl monate-A
-
-
Ile-NHSO2-AMP
-
non-hydrolyzable reaction intermediate analogue, slow-tight binding, competitive and inhibition mechanism, reversible
Ile-ol-AMP
-
-
isoleucinol adenylate
-
determination of binding structures, bound inhibitor protects against proteolytic inactivation by trypsin or chymotrypsin and specifically alters the proteolytic cleavage pattern
isoleucinyl adenylate
-
i.e. Ile-ol-AMP, nonhydrolyzable reaction intermediate analogue, competitive with respect to both ATP and Ile
isoleucinyl-adenylate
-
i.e. Ile-ol-AMP, non-hydrolyzable reaction intermediate analogue, slow-tight binding, competitive and inhibition mechanism, reversible
mupirocin
pseudomonic acid
SB-203207
-
anti-infective agent, isolated from Streptomyces NCIMB 40513, analogous to the reaction intermediate
SB-205952
Trypsin
-
proteolytic inactivation patterns, bound Ile-AMP or inhibitors isoleucinol adenylate and pseudomonic acid protect, 50fold higher concentration is needed for digestion of Ile-AMP-enzyme complex than for the free enzyme at 37°C
-
additional information
-
diverse analogues of SB-203207 are not inhibitory, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.118
L-isoleucine
mutant enzyme
0.24
ATP
-
tRNAIle aminoacylation reaction, pH 7.9, 22°C
0.005 - 0.01
L-isoleucine
0.0001
tRNAIle
additional information
additional information
-
reaction kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.35 - 18
L-isoleucine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0023
muciproin
mutant enzyme
0.00004
ethyl monate-A
-
pH 7.9, 22°C
0.000003
Ile-NHSO2-AMP
-
pH 7.9, 22°C
0.00003
Ile-ol-AMP
-
pH 7.9, 22°C
0.00003
isoleucinol adenylate
-
pH 7.9, 22°C, in complex with the enzyme and Ile, in analogy to the reaction intermediate
0.00009
isoleucinyl-adenylate
-
pH 7.9, 22°C
0.000001 - 0.00002
pseudomonic acid
0.000045
SB-205952
-
pH 7.9, 22°C
additional information
additional information
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
SYI2_STAAU
1024
0
118876
Swiss-Prot
-
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
analysis of the crystal structure with bound muciproin, PDB ID: 1FFY
purified recombinant enzyme cocrystallized with Escherichia coli tRNAIle and inhibitor muciproin, formation of the socalled editing complex, X-ray diffraction structure determination at 2.2 A resolution, and structure analysis
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
H581L/L583H
site-directed mutagenesis, slightly reduced enzyme activity
F227L
the naturally occuring mutation affects the muciprocin binding
K226T
the naturally occuring mutation affects the muciprocin binding
P187F
the naturally occuring mutation affects the muciprocin binding
Q612H
the naturally occuring mutation is involved in stabilizing the conformation of the catalytic loop containing the KMSKS motif
V588F
the naturally occuring mutation affects the Rossman fold and leads to low-level mupirocin resistance
V767D
the naturally occuring mutation affects the muciprocin binding
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
four hundred nine methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates collected in 2006 and 2007 at Madigan Army Medical Center are screened for mupirocin resistance by E test and polymerase chain reaction. No trend of increased mupirocin resistance is found when compared with subsequent years. These results show that mupirocin remains a valid infection control measure due to its unique mechanism of action and the high susceptibility rate of MRSA isolates
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Crasto, C.F.; Forrest, A.K.; Karoli, T.; March, D.R.; Mensah, L.; O'Hanlon, P.J.; Nairn, M.R.; Oldham, M.D.; Yue, W.; Banwell, M.G.; Easton, C.J.
Synthesis and activity of analogues of the isoleucyl tRNA synthetase inhibitor SB-203207
Bioorg. Med. Chem.
11
2687-2694
2003
Staphylococcus aureus, Rattus norvegicus, Staphylococcus aureus WCUH29
Manually annotated by BRENDA team
Pope, A.J.; Lapointe, J.; Mensah, L.; Benson, N.; Brown, M.J.; Moore, K.J.
Characterization of isoleucyl-tRNA synthetase from Staphylococcus aureus. I: Kinetic mechanism of the substrate activation reaction studied by transient and steady-state techniques
J. Biol. Chem.
273
31680-31690
1998
Staphylococcus aureus
Manually annotated by BRENDA team
Pope, A.J.; Moore, K.J.; McVey, M.; Mensah, L.; Benson, N.; Osbourne, N.; Broom, N.; Brown, M.J.; O'Hanlon, P.
Characterization of isoleucyl-tRNA synthetase from Staphylococcus aureus. II. Mechanism of inhibition by reaction intermediate and pseudomonic acid analogues studied using transient and steady-state kinetics
J. Biol. Chem.
273
31691-31701
1998
Staphylococcus aureus
Manually annotated by BRENDA team
Pope, A.J.; McVey, M.; Fantom, K.; Moore, K.J.
Effects of substrate and inhibitor binding on proteolysis of isoleucyl-tRNA synthetase from Staphylococcus aureus
J. Biol. Chem.
273
31702-31706
1998
Staphylococcus aureus
Manually annotated by BRENDA team
Nakama, T.; Nureki, O.; Yokoyama, S.
Structural basis for the recognition of isoleucyl-adenylate and an antibiotic, mupirocin, by isoleucyl-tRNA synthetase
J. Biol. Chem.
276
47387-47393
2001
Staphylococcus aureus (P41368), Staphylococcus aureus, Thermus thermophilus, Thermus thermophilus HB8 / ATCC 27634 / DSM 579
Manually annotated by BRENDA team
Silvian, L.F.; Wang, J.; Steitz, T.A.
Insights into editing from an Ile-tRNA synthetase structure with tRNAIle and mupirocin
Science
285
1074-1077
1999
Staphylococcus aureus (P41972), Staphylococcus aureus
Manually annotated by BRENDA team
Yang, J.A.; Park, D.W.; Sohn, J.W.; Yang, I.S.; Kim, K.H.; Kim, M.J.
Molecular analysis of isoleucyl-tRNA synthetase mutations in clinical isolates of methicillin-resistant Staphylococcus aureus with low-level mupirocin resistance
J. Korean Med. Sci.
21
827-832
2006
Staphylococcus aureus (P41972), Staphylococcus aureus
Manually annotated by BRENDA team
De Pascale, G.; Lloyd, A.J.; Schouten, J.A.; Gilbey, A.M.; Roper, D.I.; Dowson, C.G.; Bugg, T.D.
Kinetic characterisation of lipid II-Ala:alanyl tRNA ligase (MurN) from Streptococcus pneumoniae using semi-synthetic aminoacyl-lipid II substrates
J. Biol. Chem.
283
34571-34579
2008
Staphylococcus aureus
Manually annotated by BRENDA team