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Information on EC 6.1.1.12 - aspartate-tRNA ligase and Organism(s) Homo sapiens and UniProt Accession P14868
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EC Tree
6.1.1.12 aspartate-tRNA ligaseSpecify your search results
Word Map
- 6.1.1.12
- synthetases
- aminoacyl-trna
- aminoacylation
-
aspartylation
-
asparaginyl-trna
-
anticodon
- leukoencephalopathy
- trnaasn
-
aarss
-
amidotransferase
-
aspartyl-adenylate
-
microcin
-
asparaginylation
- asp-trnaasn
- glnrs
- gatcabs
-
anticodon-binding
- glutaminyl-trna
-
misacylated
-
mischarged
-
transamidation
-
nondiscriminating
- lysyl-trna
- argrs
- trnaphe
- leurs
- medicine
-
glutaminylation
- pharmacology
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
aspartyl-trna synthetase, asprs, dars2, asnrs, mitochondrial aspartyl-trna synthetase, non-discriminating aspartyl-trna synthetase, cytoplasmic aspartyl-trna synthetase, mt-asprs, discriminating asprs, d-asprs, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Antigen T5
-
-
-
-
Aspartate--tRNA ligase
-
-
-
-
Aspartic acid translase
Aspartyl ribonucleate synthetase
Aspartyl ribonucleic synthetase
-
-
-
-
Aspartyl-transfer ribonucleic acid synthetase
Aspartyl-transfer RNA synthetase
Aspartyl-tRNA synthetase
AspRS
mitochondrial aspartyl-tRNA synthetase
Synthetase, aspartyl-transfer ribonucleate
-
-
-
-
Aspartic acid translase
-
-
-
-
Aspartyl ribonucleate synthetase
-
-
-
-
Aspartyl-transfer ribonucleic acid synthetase
-
-
-
-
Aspartyl-transfer RNA synthetase
-
-
-
-
Aspartyl-tRNA synthetase
-
-
-
-
AspRS
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
esterification
Aminoacylation
esterification
-
-
-
-
Aminoacylation
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
L-aspartate:tRNAAsp ligase (AMP-forming)
-
CAS REGISTRY NUMBER
COMMENTARY
9027-32-1
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + L-aspartate + tRNAAsp
AMP + diphosphate + L-aspartyl-tRNAAsp
-
-
-
?
ATP + L-aspartate + tRNAAsp
AMP + diphosphate + aspartyl-tRNAAsp
-
-
-
-
?
ATP + L-aspartate + tRNAAsp
AMP + diphosphate + aspartyl-tRNAAsp
-
enzyme deficiency or mutation is involved in development of autosomal recessive disease leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, i.e. LBSL, often manifesting in early childhood, overview
-
-
?
ATP + L-aspartate + tRNAAsp
AMP + diphosphate + L-aspartyl-tRNAAsp
-
-
-
?
ATP + L-aspartate + tRNAAsp
AMP + diphosphate + L-aspartyl-tRNAAsp
-
-
-
-
?
ATP + L-aspartate + tRNAAsp
AMP + diphosphate + L-aspartyl-tRNAAsp
-
-
-
?
additional information
?
-
-
the N-terminal extension of the enzyme is involved in the transfer of Asp-tRNAAsp to elongation factor alpha1, the structural switch model supports the direct transfer mechanism
-
?
additional information
?
-
-
AspRS mediates stimulation of lysyl-tRNA synthetase, KRShe, with 40% stimulation when eight fold excess of AspRS is present. The non-synthetase protein from the multi-synthetase complex p38 inhibits the AspRS-mediated stimulation
-
-
?
additional information
?
-
-
mutations in the DARS2 gene cause the autosomal recessive disorder leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + L-aspartate + tRNAAsp
AMP + diphosphate + L-aspartyl-tRNAAsp
-
-
-
?
ATP + L-aspartate + tRNAAsp
AMP + diphosphate + aspartyl-tRNAAsp
-
enzyme deficiency or mutation is involved in development of autosomal recessive disease leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, i.e. LBSL, often manifesting in early childhood, overview
-
-
?
ATP + L-aspartate + tRNAAsp
AMP + diphosphate + L-aspartyl-tRNAAsp
-
-
-
?
ATP + L-aspartate + tRNAAsp
AMP + diphosphate + L-aspartyl-tRNAAsp
-
-
-
-
?
ATP + L-aspartate + tRNAAsp
AMP + diphosphate + L-aspartyl-tRNAAsp
-
-
-
?
additional information
?
-
-
the N-terminal extension of the enzyme is involved in the transfer of Asp-tRNAAsp to elongation factor alpha1, the structural switch model supports the direct transfer mechanism
-
?
additional information
?
-
-
AspRS mediates stimulation of lysyl-tRNA synthetase, KRShe, with 40% stimulation when eight fold excess of AspRS is present. The non-synthetase protein from the multi-synthetase complex p38 inhibits the AspRS-mediated stimulation
-
-
?
additional information
?
-
-
mutations in the DARS2 gene cause the autosomal recessive disorder leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.016
L-aspartate
-
Homo sapiens wild type aspartyl-tRNA synthetase, amino acids 1-500
0.00016
tRNAAsp
-
Homo sapiens wild type aspartyl-tRNA synthetase, amino acids 1-500
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
6.7
ATP
-
Homo sapiens wild type aspartyl-tRNA synthetase, amino acids 1-500, ATP-diphosphate exchange
0.22
tRNAAsp
-
Homo sapiens wild type aspartyl-tRNA synthetase, amino acids 1-500
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000079
5'-O-[N-(L-aspartyl)sulfamoyl]adenosine
-
Homo sapiens wild type aspartyl-tRNA synthetase, amino acids 1-500
0.00033
L-aspartol-adenylate
-
Homo sapiens wild type aspartyl-tRNA synthetase, amino acids 1-500
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
13.5
-
purified recombinant His6-tagged DRS-small ubiquitin-like modifier fusion enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
LBSL, i.e. leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, is a monogenic disease associated with a large variety of mutations affecting the human nuclear gene DARS2, encoding mt-AspRS, overview
physiological function
the mitochondrial aspartyl-tRNA synthetase is a key enzyme for mitochondrial translation and is correlated with leukoencephalopathy
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SYDC_HUMAN
501
0
57136
Swiss-Prot
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
secondary structure determination, structural switch model, the C-terminus adopts a regular alpha-helix with amphiphilicity, while the N-terminus shows a less-ordered structure with a flexible beta turn
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
vapor diffusion method, using 10% (m/v) PEG-3350 and 0.5M of ammonium sulfate in 25 mM Bis-Tris pH 5.5
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
C152F
D560V
hDRSDELTA32
-
N-terminal 32-residue truncated form, hDRSDELTA32, with lower thermal stability and ATP-diphosphate exchange activity, but higher aminoacylation activity. Fusion protein of glutathione-S-transferase and hDRSDELTA32 with lower thermal stability
L613F
the mutant shows reduced specific activity compared to the wild type enzyme
L626Q
the mutant shows 43fold decreased specific activity compared to the wild type enzyme
L626V
-
the mutant shows 210fold reduced activity compared to the wild-type enzyme
Q184K
R263Q
R58G
the mutant shows an increase in specific activity compared to the wild type enzyme
S45G
a naturally occuring mutation identified in patients suffering leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. The mutant enzyme is not processed due to nontranslocation of the protein
T136S
the mutant shows an increase in specific activity compared to the wild type enzyme
additional information
C152F
-
the mutant shows 14fold reduced activity compared to the wild-type enzyme
D560V
-
the mutant shows 400fold reduced activity compared to the wild-type enzyme
D560V
the mutation causes strongly reduced protein levels, the mutant shows 6fold decreased specific activity compared to the wild type enzyme
Q184K
-
the mutant shows 170fold reduced activity compared to the wild-type enzyme
Q184K
the mutant shows an increase in specific activity compared to the wild type enzyme
R263Q
-
the mutant shows 260fold reduced activity compared to the wild-type enzyme
R263Q
the mutant shows 135fold decreased specific activity compared to the wild type enzyme
additional information
-
enzyme deficiency leads to autosomal recessive disease leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation, i.e. LBSL, often manifesting in early childhood, affected individuals develop slowly progressive cerebellar ataxia, spasticity and dorsal column dysfunction, sometimes with a mild cognitive deficit or decline, phenotype, mutational analysis, overview
additional information
-
a male patient with two mutations heterogenous in the DARS2 gene, shows cerebellar, pyramidal and dorsal column dysfunctions and specific magnetic resonance imaging and characteristic magnetic resonance spectroscopy abnormalities, leukoencephalopathy with brain stem and spinal cord involvement, phenotype, overview
additional information
-
two deletion mutations in the DARS2 gene cause the autosomal recessive disorder leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation. determination of cerebellar, pyramidal and dorsal column dysfunctions and abnormalities, e.g. in in the superior cerebellar peduncles, the intraparenchymal trajectories of the trigeminal nerves, the pyramidal tracts, and the medial lemniscus, by resonance imaging, MRI, and magnetic resonance spectroscopy, MRS, phenotype, overview
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
37
-
native enzyme is stable for 24 h, half-life of truncated enzyme hDRSDELTA32 is 7 h, half-life of the fusion protein of glutathione-S-transferase and hDRSDELTA32 is 3 h
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
HiTrap chelating HP column chromatography, HiTrap Q column chromatography, and Superdex 200 gel filtration
recombinant His6-tagged DRS-SUMO and DRS-ubiquitin fusion proteins by nickel affinity chromatography from Escherichia coli strain BL21(DE3), recombinant biotin-tagged DRS-ubiquitin fusion protein by avidin affinity chromatography from Escherichia coli strain Bl21(DE3)
-
wild-type enzyme and N-terminal 32-residue truncated form (hDRS delta 32), expressed in Escherichia coli as fusion proteins linked through a thrombin cleavage site with glutathione-S-transferase
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of His6-tagged or GST-tagged enzyme in Escherichia coli strain BL21(DE3), and expression of biotin- or His6-tagged DRS-SUMO and DRS-ubiquitin fusion proteins in Escherichia coli strain BL21(DE3), since the free DRS is expressed as an inactive and insoluble protein in Escherichia coli, SUMO is a small ubiquitin-like modifier molecule
-
gene DARS2, located on chromosome 1, DNA and amino acid sequence determination and analysis, expression analysis, genotyping
-
wild-type enzyme and N-terminal 32-residues truncated form, expressed in Escherichia coli as fusion proteins linked through a thrombin cleavage site with glutathione-S-transferase
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
for designing selective inhibitors of yeast AspAS, well distinguished from mammalian AspRS, the understanding of the structural features is necessary
medicine
-
the adaption of pathogens to antibiotics calls for new target macromolecules and new types of inhibitors
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Escalante, C.; Qasba, P.K.; Yang, D.C.
Expression of human aspartyl-tRNA synthetase in COS cells
Mol. Cell. Biochem.
140
55-63
1994
Homo sapiens
Escalante, C.; Yang, D.C.
Expression of human aspartyl-tRNA synthetase in Escherichia coli. Functional analysis of the N-terminal putative amphiphilic helix
J. Biol. Chem.
268
6014-6023
1993
Bacteria, Saccharomyces cerevisiae, Homo sapiens, Mammalia
Fujiwara, S.; Lee, S.; Haruki, M.; Kanaya, S.; Takagi, M.; Imanaka, T.
Unusual enzyme characteristics of aspartyl-tRNA synthetase from hyperthermophilic archaeon Pyrococcus sp. KOD1
FEBS Lett.
394
66-70
1996
Homo sapiens, Pyrococcus sp., Pyrococcus sp. KOD1, Thermococcus kodakarensis (Q52428)
Cheong, H.K.; Park, J.Y.; Kim, E.H.; Lee, C.; Kim, S.; Kim, Y.; Choi, B.S.; Cheong, C.
Structure of the N-terminal extension of human aspartyl-tRNA synthetase: implications for its biological function
Int. J. Biochem. Cell Biol.
35
1548-1557
2003
Homo sapiens
Bonnefond, L.; Fender, A.; Rudinger-Thirion, J.; Giege, R.; Florentz, C.; Sissler, M.
Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS
Biochemistry
44
4805-4816
2005
Homo sapiens
Scheper, G.C.; van der Klok, T.; van Andel, R.J.; van Berkel, C.G.; Sissler, M.; Smet, J.; Muravina, T.I.; Serkov, S.V.; Uziel, G.; Bugiani, M.; Schiffmann, R.; Kraegeloh-Mann, I.; Smeitink, J.A.; Florentz, C.; Van Coster, R.; Pronk, J.C.; van der Knaap, M.S.
Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation
Nat. Genet.
39
534-539
2007
Homo sapiens
Guzzo, C.M.; Yang, D.C.
Systematic analysis of fusion and affinity tags using human aspartyl-tRNA synthetase expressed in E. coli
Protein Expr. Purif.
54
166-175
2007
Homo sapiens
Guzzo, C.M.; Yang, D.C.
Lysyl-tRNA synthetase interacts with EF1alpha, aspartyl-tRNA synthetase and p38 in vitro
Biochem. Biophys. Res. Commun.
365
718-723
2008
Homo sapiens
Uluc, K.; Baskan, O.; Yildirim, K.A.; Ozsahin, S.; Koseoglu, M.; Isak, B.; Scheper, G.C.; Gunal, D.I.; van der Knaap, M.S.
Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case with distinct MRI findings
J. Neurol. Sci.
273
118-122
2008
Homo sapiens
Messmer, M.; Blais, S.P.; Balg, C.; Chenevert, R.; Grenier, L.; Laguee, P.; Sauter, C.; Sissler, M.; Giege, R.; Lapointe, J.; Florentz, C.
Peculiar inhibition of human mitochondrial aspartyl-tRNA synthetase by adenylate analogs
Biochimie
91
596-603
2009
Bos taurus, Escherichia coli, Homo sapiens, Pseudomonas aeruginosa
Bour, T.; Akaddar, A.; Lorber, B.; Blais, S.; Balg, C.; Candolfi, E.; Frugier, M.
Plasmodial aspartyl-tRNA synthetases and peculiarities in Plasmodium falciparum
J. Biol. Chem.
284
18893-18903
2009
Saccharomyces cerevisiae, Homo sapiens, Plasmodium falciparum (Q8I2B1), Plasmodium falciparum
Ul-Haq, Z.; Khan, W.; Zarina, S.; Sattar, R.; Moin, S.T.
Template-based structure prediction and molecular dynamics simulation study of two mammalian aspartyl-tRNA synthetases
J. Mol. Graph. Model.
28
401-412
2010
Homo sapiens (P14868), Homo sapiens, Mus musculus (Q922B2), Mus musculus
Messmer, M.; Florentz, C.; Schwenzer, H.; Scheper, G.C.; van der Knaap, M.S.; Marechal-Drouard, L.; Sissler, M.
A human pathology-related mutation prevents import of an aminoacyl-tRNA synthetase into mitochondria
Biochem. J.
433
441-446
2011
Homo sapiens (Q6PI48), Homo sapiens
van Berge, L.; Kevenaar, J.; Polder, E.; Gaudry, A.; Florentz, C.; Sissler, M.; van der Knaap, M.S.; Scheper, G.C.
Pathogenic mutations causing LBSL affect mitochondrial aspartyl-tRNA synthetase in diverse ways
Biochem. J.
450
345-350
2013
Homo sapiens (Q6PI48), Homo sapiens
Neuenfeldt, A.; Lorber, B.; Ennifar, E.; Gaudry, A.; Sauter, C.; Sissler, M.; Florentz, C.
Thermodynamic properties distinguish human mitochondrial aspartyl-tRNA synthetase from bacterial homolog with same 3D architecture
Nucleic Acids Res.
41
2698-2708
2013
Escherichia coli, Homo sapiens (Q6PI48), Homo sapiens
Kim, K.R.; Park, S.H.; Kim, H.S.; Rhee, K.H.; Kim, B.G.; Kim, D.G.; Park, M.S.; Kim, H.J.; Kim, S.; Han, B.W.
Crystal structure of human cytosolic aspartyl-tRNA synthetase, a component of multi-tRNA synthetase complex
Proteins
81
1840-1846
2013
Homo sapiens (P14868), Homo sapiens
Schwenzer, H.; Scheper, G.; Zorn, N.; Moulinier, L.; Gaudry, A.; Leize, E.; Martin, F.; Florentz, C.; Poch, O.; Sissler, M.
Released selective pressure on a structural domain gives new insights on the functional relaxation of mitochondrial aspartyl-tRNA synthetase
Biochimie
100
18-26
2014
Homo sapiens, Mus musculus
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