6.1.1.7: alanine-tRNA ligase
This is an abbreviated version!
For detailed information about alanine-tRNA ligase, go to the full flat file.
Word Map on EC 6.1.1.7
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6.1.1.7
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aminoacylation
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synthetases
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aminoacyl-trna
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leukodystrophy
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alanylation
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mischarged
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aarss
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leukoencephalopathy
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mistranslation
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tmrnas
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charcot-marie-tooth
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noncognate
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thrrs
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threonyl-trna
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minihelix
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seryl-trna
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anti-pl-12
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valrs
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misactivation
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microhelix
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ilers
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trans-translation
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molecular biology
- 6.1.1.7
- aminoacylation
- synthetases
- aminoacyl-trna
- leukodystrophy
-
alanylation
-
mischarged
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aarss
- leukoencephalopathy
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mistranslation
- tmrnas
- charcot-marie-tooth
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noncognate
- thrrs
- threonyl-trna
- minihelix
- seryl-trna
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anti-pl-12
- valrs
-
misactivation
- microhelix
- ilers
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trans-translation
- molecular biology
Reaction
Synonyms
AARS2, Ala-tRNA synthetase, ALA1, ALA2, Alanine transfer RNA synthetase, Alanine translase, Alanine tRNA synthetase, Alanine--tRNA ligase, Alanine-transfer RNA ligase, alanine-tRNA ligase, alanyl tRNA ligase, Alanyl-transfer ribonucleate synthetase, Alanyl-transfer ribonucleic acid synthetase, Alanyl-transfer RNA synthetase, alanyl-tRNA ligase, alanyl-tRNA synthase, Alanyl-tRNA synthetase, alanyltRNA synthetase, AlaRS, mitochondrial alanyl-tRNA synthetase, More, mtAlaRS, MurM, MurN, Synthase, alanyl-transfer ribonucleate
ECTree
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General Information
General Information on EC 6.1.1.7 - alanine-tRNA ligase
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evolution
malfunction
physiological function
additional information
the enzyme belongs to the class IIa aminoacyl-tRNA synthestase family
evolution
the enzyme belongs to the class IIa aminoacyl-tRNA synthestase family. Divergent alanyl-tRNA synthetase genes of Vanderwaltozyma polyspora descended from a common ancestor through whole-genome duplication followed by asymmetric evolution. Cytoplasmic and mitochondrial forms of a eukaryotic aminoacyl-tRNA synthetase (aaRS) are generally encoded by two distinct nuclear genes, one of eukaryotic origin and the other of mitochondrial origin. In most known yeasts, only the mitochondrial-origin alanyl-tRNA synthetase (AlaRS) gene is retained and plays a dual-functional role. In contrast, the yeast Tetrapisispora phaffii possesses two significantly diverged AlaRS gene homologues, one encoding the cytoplasmic form and the other its mitochondrial counterpart. Phylogenetic relationships of yeast AlaRSs, overview
evolution
the enzyme belongs to the class IIa aminoacyl-tRNA synthestase family. Divergent alanyl-tRNA synthetase genes of Vanderwaltozyma polyspora descended from a common ancestor through whole-genome duplication followed by asymmetric evolution. Cytoplasmic and mitochondrial forms of a eukaryotic aminoacyl-tRNA synthetase (aaRS) are generally encoded by two distinct nuclear genes, one of eukaryotic origin and the other of mitochondrial origin. In most known yeasts, only the mitochondrial-origin alanyl-tRNA synthetase (AlaRS) gene is retained and plays a dual-functional role. In contrast, the yeast Vanderwaltozyma polyspora possesses two significantly diverged AlaRS gene homologues, one encoding the cytoplasmic form and the other its mitochondrial counterpart. Clever selection of transcription and translation initiation sites enables the two isoforms to be localized and thus functional in their respective cellular compartments. But the two isoforms can also be stably expressed and function in the reciprocal compartments by insertion or removal of a mitochondrial targeting signal. Synteny and phylogeny analyses reveal that the AlaRS homologues of Vanderwaltozyma polyspora arose from a dual-functional common ancestor through whole-genome duplication (WGD). Moreover, the mitochondrial form has higher synonymous (1.6fold) and nonsynonymous (2.8fold) substitution rates than does its cytoplasmic counterpart, presumably due to a lesser constraint imposed on components of the mitochondrial translational apparatus. Asymmetric evolution confers the divergence between the AlaRS paralogues of Vanderwaltozyma polyspora. Phylogenetic relationships of yeast AlaRSs, overview
evolution
the enzyme belongs to the class IIa aminoacyl-tRNA synthestase family. Divergent alanyl-tRNA synthetase genes of Vanderwaltozyma polyspora descended from a common ancestor through whole-genome duplication followed by asymmetric evolution. Cytoplasmic and mitochondrial forms of a eukaryotic aminoacyl-tRNA synthetase (aaRS) are generally encoded by two distinct nuclear genes, one of eukaryotic origin and the other of mitochondrial origin. In most known yeasts, only the mitochondrial-origin alanyl-tRNA synthetase (AlaRS) gene is retained and plays a dual-functional role. The AlaRS homologues of Saccharomyces cerevisiae arose from a dual-functional common ancestor through whole-genome duplication (WGD), but retains only one copy of the AlaRS gene. Phylogenetic relationships of yeast AlaRSs, overview
evolution
the enzyme belongs to the class IIa aminoacyl-tRNA synthetase family. Divergent alanyl-tRNA synthetase genes of Vanderwaltozyma polyspora descended from a common ancestor through whole-genome duplication followed by asymmetric evolution. Cytoplasmic and mitochondrial forms of a eukaryotic aminoacyl-tRNA synthetase (aaRS) are generally encoded by two distinct nuclear genes, one of eukaryotic origin and the other of mitochondrial origin. In most known yeasts, only the mitochondrial-origin alanyl-tRNA synthetase (AlaRS) gene is retained and plays a dual-functional role. In contrast, the yeast Tetrapisispora phaffii possesses two significantly diverged AlaRS gene homologues, one encoding the cytoplasmic form and the other its mitochondrial counterpart. Phylogenetic relationships of yeast AlaRSs, overview
evolution
the enzyme is constituted by three domains with an evolutionarily conserved modular arrangement: the N-terminal aminoacylation domain, the editing domain and the C-terminal domain (C-Ala). Alanyl-tRNA synthetases (AlaRSs) belong to class-II aminoacyl-tRNA synthetases
evolution
the sequence of appended C-terminal domain (C-Ala) of enzyme AlaRS diverged widely in the evolutionary progression to humans. During evolution, 19 aaRSs expanded by acquiring novel noncatalytic appended domains, which are absent from bacteria and many lower eukaryotes but confer extracellular and nuclear functions in higher organisms. AlaRS is the single exception, with an appended C-terminal domain (C-Ala) that is conserved from prokaryotes to humans but with a wide sequence divergence. In human cells, C-Ala is also a splice variant of AlaRS. Crystal structures of two forms of human C-Ala, and small-angle X-ray scattering of AlaRS, show that the large sequence divergence of human C-Ala reshaped C-Ala in a way that changed the global architecture of AlaRS. This reshaping removed the role of C-Ala in prokaryotes for docking tRNA and instead repurposed it to form a dimer interface presenting a DNA-binding groove. This groove cannot form with the bacterial ortholog. Direct DNA binding by human C-Ala, but not by bacterial C-Ala. Instead of acquiring a special appended domain, a new AlaRS architecture has benn created by diversifying a preexisting domain
evolution
Vanderwaltozyma polyspora ATCC 22028 / DSM 70294
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the enzyme belongs to the class IIa aminoacyl-tRNA synthestase family. Divergent alanyl-tRNA synthetase genes of Vanderwaltozyma polyspora descended from a common ancestor through whole-genome duplication followed by asymmetric evolution. Cytoplasmic and mitochondrial forms of a eukaryotic aminoacyl-tRNA synthetase (aaRS) are generally encoded by two distinct nuclear genes, one of eukaryotic origin and the other of mitochondrial origin. In most known yeasts, only the mitochondrial-origin alanyl-tRNA synthetase (AlaRS) gene is retained and plays a dual-functional role. In contrast, the yeast Vanderwaltozyma polyspora possesses two significantly diverged AlaRS gene homologues, one encoding the cytoplasmic form and the other its mitochondrial counterpart. Clever selection of transcription and translation initiation sites enables the two isoforms to be localized and thus functional in their respective cellular compartments. But the two isoforms can also be stably expressed and function in the reciprocal compartments by insertion or removal of a mitochondrial targeting signal. Synteny and phylogeny analyses reveal that the AlaRS homologues of Vanderwaltozyma polyspora arose from a dual-functional common ancestor through whole-genome duplication (WGD). Moreover, the mitochondrial form has higher synonymous (1.6fold) and nonsynonymous (2.8fold) substitution rates than does its cytoplasmic counterpart, presumably due to a lesser constraint imposed on components of the mitochondrial translational apparatus. Asymmetric evolution confers the divergence between the AlaRS paralogues of Vanderwaltozyma polyspora. Phylogenetic relationships of yeast AlaRSs, overview
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evolution
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the enzyme is constituted by three domains with an evolutionarily conserved modular arrangement: the N-terminal aminoacylation domain, the editing domain and the C-terminal domain (C-Ala). Alanyl-tRNA synthetases (AlaRSs) belong to class-II aminoacyl-tRNA synthetases
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enzyme mutations are associated with infantile mitochondrial cardiomyopathy
malfunction
importance of the mtARS proteins for mitochondrial pathophysiology since nearly every nuclear gene for mtARS (out of 19) is recognized as a disease gene for mitochondrial disease. Mutations in the AARS2 gene for mitochondrial alanyl-tRNA synthetase (mtAlaRS) is observed both in patients with infantile-onset cardiomyopathy and in patients with childhood to adulthood-onset leukoencephalopathy. The cardiomyopathy phenotype results from a single allele, causing an amino acid change R592W in the editing domain of AARS2, whereas the leukodystrophy mutations are located in other domains of the synthetase. All mutations reduce the aminoacylation activity of the synthetase, because all mtAlaRS domains contribute to tRNA binding for aminoacylation. The cardiomyopathy mutations severely compromise aminoacylation whereas partial activity is retained by the mutation combinations found in the leukodystrophy patients. Molecular basis of the distinct tissue-specific phenotypic outcomes of enzyme mutantions, structure analysis and homology modeling, overview
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the relatively modest specificity of the AlaRS editing domain may provide a rationale for the widespread phylogenetic distribution of AlaX free-standing editing domains, thereby contributing a further mechanism to lower concentrations of misacylated tRNAAla
physiological function
alanyl-tRNA synthetases (AlaRSs) play an essential role in the early events of protein synthesis by catalyzing the conjugation of amino acids to their cognate transfer RNAs. The C-terminal domain, C-Ala, plays an essential role in enzyme activity
physiological function
the accuracy of mitochondrial protein synthesis is dependent on the coordinated action of nuclear-encoded mitochondrial aminoacyl-tRNA synthetases (mtARSs) and the mitochondrial DNA-encoded tRNAs. The mitochondrial alanyl-tRNA synthetase (mtAlaRS) differs from the other mtARSs because in addition to the aminoacylation domain, it has a conserved editing domain for deacylating tRNAs that have been mischarged within correct amino acids
physiological function
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alanyl-tRNA synthetases (AlaRSs) play an essential role in the early events of protein synthesis by catalyzing the conjugation of amino acids to their cognate transfer RNAs. The C-terminal domain, C-Ala, plays an essential role in enzyme activity
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enzyme structure modeling, analysis of the contact surface between linker safety belt, and beta-barrel of the editing domain in modeled human mitochondrial AlaRS, overview
additional information
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enzyme structure modeling, analysis of the contact surface between linker safety belt, and beta-barrel of the editing domain in modeled human mitochondrial AlaRS, overview
additional information
the near complete NMR resonance assignment of the 122 amino acid C-Ala domain from Bizionia argentinensis is determined, enzyme structure homology modeling using the X-ray structure of Aquifex aeolicus AlaRS C-Ala domain
additional information
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the near complete NMR resonance assignment of the 122 amino acid C-Ala domain from Bizionia argentinensis is determined, enzyme structure homology modeling using the X-ray structure of Aquifex aeolicus AlaRS C-Ala domain
additional information
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the near complete NMR resonance assignment of the 122 amino acid C-Ala domain from Bizionia argentinensis is determined, enzyme structure homology modeling using the X-ray structure of Aquifex aeolicus AlaRS C-Ala domain
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