tRNA synthetases catalyze the ligation of tRNAs to their cognate amino acids in an ATP-dependent manner. The reaction proceeds in two steps. First, amino acid and ATP form an aminoacyl adenylate molecule, releasing pyrophosphate. The aminoacyl adenylate remains associated with the synthetase enzyme where, in the second step it reacts with tRNA to form aminoacyl tRNA and AMP. The rapid hydrolysis of pyrophosphate makes these reactions essentially irreversible under physiological conditions (Fersht and Kaethner 1976a). Specificity of the tRNA charging reactions is achieved both by specific recognition of amino acid and tRNA substrates by the synthetase, and by an editing process in which incorrect aminoacyl adenylate molecules (e.g., valyl adenylate associated with isoleucyl tRNA synthetase) are hydrolyzed rather than conjugated to tRNAs in the second step of the reaction (Baldwin and Berg 1966a,b; Fersht and Kaethner 1976b). The tRNA synthetases can be divided into two structural classes based on conserved amino acid sequence features (Burnbaum and Schimmel 1991).
A single synthetase mediates the charging of all of the tRNA species specific for any one amino acid but, with three exceptions, glycine, lysine, and glutamine, the synthetase that catalyzes aminoacylation of mitochondrial tRNAs is encoded by a different gene than the one that acts on mitochondrial tRNAs. Both mitochondrial and cytosolic tRNA synthetase enzymes are encoded by genes in the nuclear genome.<p>A number of tRNA synthetases are known to have functions distinct from tRNA charging (reviewed by Park et al. 2005). Additionally, mutations in several of the tRNA synthetases, often affecting protein domains that are dispensable in vitro for aminoacyl tRNA synthesis, are associated with a diverse array of neurological and other diseases (Antonellis and Green 2008; Park et al. 2008). These findings raise interest into the role of these enzymes in human development and disease.<p>
View original pathway at:Reactome.</div>
Vilalta A, Donovan D, Wood L, Vogeli G, Yang DC.; ''Cloning, sequencing and expression of a cDNA encoding mammalian valyl-tRNA synthetase.''; PubMedEurope PMCScholia
Kaminska M, Shalak V, Mirande M.; ''The appended C-domain of human methionyl-tRNA synthetase has a tRNA-sequestering function.''; PubMedEurope PMCScholia
Spencer AC, Heck A, Takeuchi N, Watanabe K, Spremulli LL.; ''Characterization of the human mitochondrial methionyl-tRNA synthetase.''; PubMedEurope PMCScholia
Burbaum JJ, Schimmel P.; ''Structural relationships and the classification of aminoacyl-tRNA synthetases.''; PubMedEurope PMCScholia
O'Hanlon TP, Raben N, Miller FW.; ''A novel gene oriented in a head-to-head configuration with the human histidyl-tRNA synthetase (HRS) gene encodes an mRNA that predicts a polypeptide homologous to HRS.''; PubMedEurope PMCScholia
Bullard JM, Cai YC, Spremulli LL.; ''Expression and characterization of the human mitochondrial leucyl-tRNA synthetase.''; PubMedEurope PMCScholia
Lamour V, Quevillon S, Diriong S, N'Guyen VC, Lipinski M, Mirande M.; ''Evolution of the Glx-tRNA synthetase family: the glutaminyl enzyme as a case of horizontal gene transfer.''; PubMedEurope PMCScholia
Park SG, Schimmel P, Kim S.; ''Aminoacyl tRNA synthetases and their connections to disease.''; PubMedEurope PMCScholia
Jordanova A, Irobi J, Thomas FP, Van Dijck P, Meerschaert K, Dewil M, Dierick I, Jacobs A, De Vriendt E, Guergueltcheva V, Rao CV, Tournev I, Gondim FA, D'Hooghe M, Van Gerwen V, Callaerts P, Van Den Bosch L, Timmermans JP, Robberecht W, Gettemans J, Thevelein JM, De Jonghe P, Kremensky I, Timmerman V.; ''Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy.''; PubMedEurope PMCScholia
Shiba K, Ripmaster T, Suzuki N, Nichols R, Plotz P, Noda T, Schimmel P.; ''Human alanyl-tRNA synthetase: conservation in evolution of catalytic core and microhelix recognition.''; PubMedEurope PMCScholia
Edvardson S, Shaag A, Kolesnikova O, Gomori JM, Tarassov I, Einbinder T, Saada A, Elpeleg O.; ''Deleterious mutation in the mitochondrial arginyl-transfer RNA synthetase gene is associated with pontocerebellar hypoplasia.''; PubMedEurope PMCScholia
Curbo S, Lagier-Tourenne C, Carrozzo R, Palenzuela L, Lucioli S, Hirano M, Santorelli F, Arenas J, Karlsson A, Johansson M.; ''Human mitochondrial pyrophosphatase: cDNA cloning and analysis of the gene in patients with mtDNA depletion syndromes.''; PubMedEurope PMCScholia
Fersht AR, Kaethner MM.; ''Mechanism of aminoacylation of tRNA. Proof of the aminoacyl adenylate pathway for the isoleucyl- and tyrosyl-tRNA synthetases from Escherichia coli K12.''; PubMedEurope PMCScholia
Fisher RA, Turner BM, Dorkin HL, Harris H.; ''Studies on human erythrocyte inorganic pyrophosphatase.''; PubMedEurope PMCScholia
Scheper GC, van der Klok T, van Andel RJ, van Berkel CG, Sissler M, Smet J, Muravina TI, Serkov SV, Uziel G, Bugiani M, Schiffmann R, Krägeloh-Mann I, Smeitink JA, Florentz C, Van Coster R, Pronk JC, van der Knaap MS.; ''Mitochondrial aspartyl-tRNA synthetase deficiency causes leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation.''; PubMedEurope PMCScholia
Wolfe CL, Warrington JA, Davis S, Green S, Norcum MT.; ''Isolation and characterization of human nuclear and cytosolic multisynthetase complexes and the intracellular distribution of p43/EMAPII.''; PubMedEurope PMCScholia
Degoul F, Brulé H, Cepanec C, Helm M, Marsac C, Leroux J, Giegé R, Florentz C.; ''Isoleucylation properties of native human mitochondrial tRNAIle and tRNAIle transcripts. Implications for cardiomyopathy-related point mutations (4269, 4317) in the tRNAIle gene.''; PubMedEurope PMCScholia
Jorgensen R, Søgaard TM, Rossing AB, Martensen PM, Justesen J.; ''Identification and characterization of human mitochondrial tryptophanyl-tRNA synthetase.''; PubMedEurope PMCScholia
Baldwin AN, Berg P.; ''Transfer ribonucleic acid-induced hydrolysis of valyladenylate bound to isoleucyl ribonucleic acid synthetase.''; PubMedEurope PMCScholia
Antonellis A, Ellsworth RE, Sambuughin N, Puls I, Abel A, Lee-Lin SQ, Jordanova A, Kremensky I, Christodoulou K, Middleton LT, Sivakumar K, Ionasescu V, Funalot B, Vance JM, Goldfarb LG, Fischbeck KH, Green ED.; ''Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V.''; PubMedEurope PMCScholia
Park SG, Ewalt KL, Kim S.; ''Functional expansion of aminoacyl-tRNA synthetases and their interacting factors: new perspectives on housekeepers.''; PubMedEurope PMCScholia
Ling C, Yao YN, Zheng YG, Wei H, Wang L, Wu XF, Wang ED.; ''The C-terminal appended domain of human cytosolic leucyl-tRNA synthetase is indispensable in its interaction with arginyl-tRNA synthetase in the multi-tRNA synthetase complex.''; PubMedEurope PMCScholia
Moor N, Linshiz G, Safro M.; ''Cloning and expression of human phenylalanyl-tRNA synthetase in Escherichia coli: comparative study of purified recombinant enzymes.''; PubMedEurope PMCScholia
Yang XL, Otero FJ, Skene RJ, McRee DE, Schimmel P, Ribas de Pouplana L.; ''Crystal structures that suggest late development of genetic code components for differentiating aromatic side chains.''; PubMedEurope PMCScholia
Beaulande M, Tarbouriech N, Härtlein M.; ''Human cytosolic asparaginyl-tRNA synthetase: cDNA sequence, functional expression in Escherichia coli and characterization as human autoantigen.''; PubMedEurope PMCScholia
Vincent C, Tarbouriech N, Härtlein M.; ''Genomic organization, cDNA sequence, bacterial expression, and purification of human seryl-tRNA synthase.''; PubMedEurope PMCScholia
Pan F, Lee HH, Pai SH, Lo KY.; ''Purification and subunit structure studies of human placental threonyl-tRNA synthetase.''; PubMedEurope PMCScholia
Yu Y, Liu Y, Shen N, Xu X, Xu F, Jia J, Jin Y, Arnold E, Ding J.; ''Crystal structure of human tryptophanyl-tRNA synthetase catalytic fragment: insights into substrate recognition, tRNA binding, and angiogenesis activity.''; PubMedEurope PMCScholia
Escalante C, Yang DC.; ''Expression of human aspartyl-tRNA synthetase in Escherichia coli. Functional analysis of the N-terminal putative amphiphilic helix.''; PubMedEurope PMCScholia
Bange FC, Flohr T, Buwitt U, Böttger EC.; ''An interferon-induced protein with release factor activity is a tryptophanyl-tRNA synthetase.''; PubMedEurope PMCScholia
Shiba K, Suzuki N, Shigesada K, Namba Y, Schimmel P, Noda T.; ''Human cytoplasmic isoleucyl-tRNA synthetase: selective divergence of the anticodon-binding domain and acquisition of a new structural unit.''; PubMedEurope PMCScholia
Pynes GD, Younathan ES.; ''Purification and some properties of inorganic pyrophosphatase from human erythrocytes.''; PubMedEurope PMCScholia
Rubin BY, Anderson SL, Xing L, Powell RJ, Tate WP.; ''Interferon induces tryptophanyl-tRNA synthetase expression in human fibroblasts.''; PubMedEurope PMCScholia
Davidson E, Caffarella J, Vitseva O, Hou YM, King MP.; ''Isolation of two cDNAs encoding functional human cytoplasmic cysteinyl-tRNA synthetase.''; PubMedEurope PMCScholia
Baldwin AN, Berg P.; ''Purification and properties of isoleucyl ribonucleic acid synthetase from Escherichia coli.''; PubMedEurope PMCScholia
Thuillier L.; ''Purification and kinetic properties of human erythrocyte Mg2+-dependent inorganic pyrophosphatase.''; PubMedEurope PMCScholia
Lee JW, Beebe K, Nangle LA, Jang J, Longo-Guess CM, Cook SA, Davisson MT, Sundberg JP, Schimmel P, Ackerman SL.; ''Editing-defective tRNA synthetase causes protein misfolding and neurodegeneration.''; PubMedEurope PMCScholia
Bullard JM, Cai YC, Demeler B, Spremulli LL.; ''Expression and characterization of a human mitochondrial phenylalanyl-tRNA synthetase.''; PubMedEurope PMCScholia
Kaiser E, Hu B, Becher S, Eberhard D, Schray B, Baack M, Hameister H, Knippers R.; ''The human EPRS locus (formerly the QARS locus): a gene encoding a class I and a class II aminoacyl-tRNA synthetase.''; PubMedEurope PMCScholia
Bonnefond L, Fender A, Rudinger-Thirion J, Giegé R, Florentz C, Sissler M.; ''Toward the full set of human mitochondrial aminoacyl-tRNA synthetases: characterization of AspRS and TyrRS.''; PubMedEurope PMCScholia
Fersht AR, Kaethner MM.; ''Enzyme hyperspecificity. Rejection of threonine by the valyl-tRNA synthetase by misacylation and hydrolytic editing.''; PubMedEurope PMCScholia
Yokogawa T, Shimada N, Takeuchi N, Benkowski L, Suzuki T, Omori A, Ueda T, Nishikawa K, Spremulli LL, Watanabe K.; ''Characterization and tRNA recognition of mammalian mitochondrial seryl-tRNA synthetase.''; PubMedEurope PMCScholia
Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S.; ''Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex.''; PubMedEurope PMCScholia
HARS (cytosolic histidyl tRNA synthetase) catalyzes the reaction of histidine, tRNA(His), and ATP to form His-tRNA(His), AMP, and pyrophosphate (Lee et al. 2002).
FARS (cytosolic phenylalanyl tRNA synthetase) catalyzes the reaction of phenylalanine, tRNA(Phe), and ATP to form Phe-tRNA(Phe), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a heterotetramer of two alpha and two beta subunits (Moor et al. 2002).
Multifunctional EPRS (cytosolic glutamyl prolyl tRNA synthetase) catalyzes the reaction of glutamate, tRNA(Glu), and ATP to form Glu tRNA(Glu), AMP, and pyrophosphate. The same enzyme also catalyzes the charging of tRNA(Pro) with proline. The enzyme is found in the cell as a component of the mutienzyme aminoacyl tRNA synthetase complex (Kaiser et al. 1994).
AARS (cytosolic alanyl tRNA synthetase) catalyzes the reaction of alanine, tRNA(ala), and ATP to form Ala tRNA(Ala), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a monomer (Shiba et al. 1995). A mutation in the editing domain of the mouse Aars gene results in misincorporation of non-cognate amino acids into cellular proteins. This is associated with protein misfolding in Purkinje cells and a phenotype consistent with human ataxia (Lee et al. 2006).
Multifunctional EPRS (cytosolic glutamyl-prolyl tRNA synthetase) catalyzes the reaction of proline, tRNA(Pro), and ATP to form Pro-tRNA(Pro), AMP, and pyrophosphate. The same enzyme also catalyzes the charging of tRNA(Glu) with glutamate. The enzyme is found in the cell as a component of the mutienzyme aminoacyl-tRNA synthetase complex (Kaiser et al. 1994).
DARS (cytosolic aspartyl tRNA synthetase) catalyzes the reaction of aspartate, tRNA(Asp), and ATP to form Asp-tRNA(Asp), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a homodimer found in the cell as a component of the mutienzyme aminoacyl-tRNA synthetase complex (Escalante and Yang 1993).
CARS (cytosolic cysteinyl tRNA synthetase) catalyzes the reaction of cysteine, tRNA(cys), and ATP to form Cys-tRNA(Cys), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a homomultimer, probably a dimer (Davidson et al. 2001).
IARS (cytosolic aspartyl tRNA synthetase) catalyzes the reaction of isoleucine, tRNA(Ile), and ATP to form Ile-tRNA(Ile), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is found in the cell as a component of the mutienzyme aminoacyl-tRNA synthetase complex (Shiba et al. 1994).
LARS (cytosolic leucyl tRNA synthetase) catalyzes the reaction of leucine, tRNA(Leu), and ATP to form Leu-tRNA(Leu), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is found in the cell as a component of the mutienzyme aminoacyl-tRNA synthetase complex (Ling et al. 2005).
WARS (cytosolic tryptophanyl tRNA synthetase) catalyzes the reaction of tryptophan, tRNA(Trp), and ATP to form Trp-tRNA(Trp), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a homodimer (Bange et al. 1992; Rubin et al. 1991; Yu et al. 2004).
YARS (cytosolic tyrosyl tRNA synthetase) catalyzes the reaction of tyrosine, tRNA(Tyr), and ATP to form Tyr tRNA(Tyr), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a homodimer (Yang et al. 2003). Mutations in the YARS gene are associated with dominant-intermediate Charcot-Marie-Tooth disease – a form of peripheral neuropathy characterized by axon and Schwann cell dysfunction (Jordanova et al. 2006).
QARS (cytosolic glutaminyl tRNA synthetase) catalyzes the reaction of glutamine, tRNA(Gln), and ATP to form Gln-tRNA(Gln), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is found in the cell as a component of the mutienzyme aminoacyl-tRNA synthetase complex. The same gene encodes both the cytosolic and mitochondrial QARS enzymes (Lamour et al. 1994).
SARS (cytosolic seryl tRNA synthetase) catalyzes the reaction of serine, tRNA(Ser), and ATP to form Ser-tRNA(Ser), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a homodimer (Hartlein and Cusack 1995; Vincent et al. 1997).
RARS (cytosolic arginyl tRNA synthetase) catalyzes the reaction of arginine, tRNA(Arg), and ATP to form Arg-tRNA(Arg), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a monomer found in the cell as a component of the mutienzyme aminoacyl-tRNA synthetase complex (Ling et al. 2005).
MARS (cytosolic methionyl tRNA synthetase) catalyzes the reaction of methionine, tRNA(Met), and ATP to form Met-tRNA(Met), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a monomer found in the cell as a component of the mutienzyme aminoacyl-tRNA synthetase complex (Kaminska et al. 2001).
NARS (cytosolic asparaginyl tRNA synthetase) catalyzes the reaction of asparagine, tRNA(Asn), and ATP to form Asn-tRNA(Asn), AMP, and pyrophosphate. The enzyme is a class I tRNA synthetase (Beaulande et al. 1998).
TARS (cytosolic threonyl tRNA synthetase) catalyzes the reaction of threonine, tRNA(Thr), and ATP to form Thr-tRNA(Thr), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a homodimer (Pan et al. 1982).
KARS (cytosolic lysyl tRNA synthetase) catalyzes the reaction of lysine, tRNA(Lys), and ATP to form Lys-tRNA(Lys), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a homodimer found in the cell as a component of the mutienzyme aminoacyl-tRNA synthetase complex. The same gene encodes both cytosolic and mitochondrial KARS enzymes (Shiba et al. 1997).
VARS (cytosolic valyl tRNA synthetase) catalyzes the reaction of valine, tRNA(Val), and ATP to form Val-tRNA(Val), AMP, and pyrophosphate. The enzyme is a class I tRNA synthetase (Vilalta et al. 1993).
GARS (cytosolic glycyl tRNA synthetase) catalyzes the reaction of glycine, tRNA(Gly), and ATP to form Gly tRNA(Gly), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a dimer. Cytosolic and mitochondrial glycyl tRNA synthetase enzymes are both encoded by the same gene; the cytosolic protein lacks an aminoterminal 54 residue sequence found in the mitochondrial protein. Mutations in GARS are associated with Charcot Marie Tooth disease and distal spinal muscular atrophy, two diseases characterized by axonal dysfunction (Antonellis et al. 2006)
MARS2 (mitochondrial methionyl tRNA synthetase) catalyzes the reaction of methionine, mitochondrial tRNA(Met), and ATP to form Met-tRNA(Met), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a monomer (Spencer et al. 2004).
CARS2 (mitochondrial cysteinyl tRNA synthetase) catalyzes the reaction of cysteine, mitochondrial tRNA(Cys), and ATP to form Cys-tRNA(Cys), AMP, and pyrophosphate. The CARS2 gene has been identified by computational analysis of the human genome sequence; its function has been inferred from those of the biochemically characterized mitochondrial aspartyl and tyrosyl tRNA synthetases (Bonnefond et al. 2005).
YARS2 (mitochondrial tyrosyl tRNA synthetase) catalyzes the reaction of tyrosine, mitochondrial tRNA(Tyr), and ATP to form Tyr-tRNA(Tyr), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a homodimer (Bonnefond et al. 2005).
IARS2 (mitochondrial isoleucyl tRNA synthetase) catalyzes the reaction of isoleucine, mitochondrial tRNA(Ile), and ATP to form Ile-tRNA(Ile), AMP, and pyrophosphate. The enzyme is a class I tRNA synthetase (Degoul et al. 1995).
AARS2 (mitochondrial alanyl tRNA synthetase) catalyzes the reaction of alanine, mitochondrial tRNA(Ala), and ATP to form Ala-tRNA(Ala), AMP, and pyrophosphate. The AARS2 gene has been identified by computational analysis of the human genome sequence; its function has been inferred from those of the biochemically characterized mitochondrial aspartyl and tyrosyl tRNA synthetases (Bonnefond et al. 2005).
PARS2 (mitochondrial prolyl tRNA synthetase) catalyzes the reaction of proline, mitochondrial tRNA(Pro), and ATP to form Pro-tRNA(Pro), AMP, and pyrophosphate. The PARS2 gene has been identified by computational analysis of the human genome sequence; its function has been inferred from those of the biochemically characterized mitochondrial aspartyl and tyrosyl tRNA synthetases (Bonnefond et al. 2005).
VARS2 (mitochondrial valyl tRNA synthetase) catalyzes the reaction of valine, mitochondrial tRNA(val), and ATP to form Val-tRNA(Val), AMP, and pyrophosphate. The VARS2 gene has been identified by computational analysis of the human genome sequence; its function has been inferred from those of the biochemically characterized mitochondrial aspartyl and tyrosyl tRNA synthetases (Bonnefond et al. 2005).
LARS2 (mitochondrial leucyl tRNA synthetase) catalyzes the reaction of leucine, mitochondrial tRNA(Leu), and ATP to form Leu-tRNA(Leu), AMP, and pyrophosphate. The enzyme, a class I tRNA synthetase, is a monomer (Bullard et al. 2000).
TARS2 (mitochondrial threonyl tRNA synthetase) catalyzes the reaction of threonine, mitochondrial tRNA(Thr), and ATP to form Thr-tRNA(Thr), AMP, and pyrophosphate. The TARS2 gene has been identified by computational analysis of the human genome sequence; its function has been inferred from those of the biochemically characterized mitochondrial aspartyl and tyrosyl tRNA synthetases (Bonnefond et al. 2005).
FARS2 (mitochondrial phenylalanyl tRNA synthetase) catalyzes the reaction of phenylalanine, mitochondrial tRNA(Phe), and ATP to form Phe-tRNA(Phe), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a monomer (Bullard et al. 1999).
EARS2 (mitochondrial glutamyl tRNA synthetase) catalyzes the reaction of glutamate, mitochondrial tRNA(Glu), and ATP to form Glu-tRNA(Glu), AMP, and pyrophosphate. The EARS2 gene has been identified by computational analysis of the human genome sequence; its function has been inferred from those of the biochemically characterized mitochondrial aspartyl and tyrosyl tRNA synthetases (Bonnefond et al. 2005).
WARS2 (mitochondrial tryptophanyl tRNA synthetase) catalyzes the reaction of tryptophan, mitochondrial tRNA(Trp), and ATP to form Trp-tRNA(Trp), AMP, and pyrophosphate. The enzyme is a class I tRNA synthetase (Jorgensen et al. 2000).
RARS2 (mitochondrial arginyl tRNA synthetase) catalyzes the reaction of arginine, mitochondrial tRNA(Arg), and ATP to form Arg tRNA(Arg), AMP, and pyrophosphate. The enzyme is a class I tRNA synthetase. Homozygosity for RARS2 mutations has been associated with pontocerebellar hypoplasia – a disease characterized by a severe reduction in cerebellum and brainstem size (Edvardson et al. 2007).
NARS2 (mitochondrial asparaginyl tRNA synthetase) catalyzes the reaction of asparagine, mitochondrial tRNA(Asn), and ATP to form Asn-tRNA(Asn), AMP, and pyrophosphate. The NARS2 gene has been identified by computational analysis of the human genome sequence; its function has been inferred from those of the biochemically characterized mitochondrial aspartyl and tyrosyl tRNA synthetases (Bonnefond et al. 2005).
DARS2 (mitochondrial aspartyl tRNA synthetase) catalyzes the reaction of aspartate, mitochondrial tRNA(Asp), and ATP to form Asp tRNA(Asp), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a homodimer (Bonnefond et al. 2005). Homozygosity for DARS2 mutations is associated with leukoencephalopathy with brainstem and spinal cord involvement plus lactate elevation (Scheper et al 2007).
KARS (mitochondrial lysyl tRNA synthetase) catalyzes the reaction of lysine, tRNA(Lys), and ATP to form Lys-tRNA(Lys), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a homodimer. The same gene encodes both cytosolic and mitochondrial KARS enzymes (Shiba et al. 1997).
HARS2 (mitochondrial histidyl tRNA synthetase) catalyzes the reaction of histidine, mitochondrial tRNA(His), and ATP to form His-tRNA(His), AMP, and pyrophosphate. The enzyme is a class II tRNA synthetase (O'Hanlon et al. 1995).
SARS2 (mitochondrial seryl tRNA synthetase) catalyzes the reaction of serine, mitochondrial tRNA(Ser), and ATP to form Ser-tRNA(Ser), AMP, and pyrophosphate. SARS2 is a class II tRNA synthetase inferred from the biochemical properties of its bovine homologue to function as a dimer (Yokogawa et al. 2000).
GARS (mitochondrial glycyl tRNA synthetase) catalyzes the reaction of glycine, tRNA(Gly), and ATP to form Gly-tRNA(Gly), AMP, and pyrophosphate. The enzyme, a class II tRNA synthetase, is a dimer. Cytosolic and mitochondrial glycyl tRNA synthetase enzymes are both encoded by the same gene; the cytosolic protein lacks an aminoterminal 54-residue sequence found in the mitochondrial protein. Mutations in GARS are associated with Charcot-Marie-Tooth disease (Antonellis et al. 2007).
QARS (mitochondrial glutaminyl tRNA synthetase) catalyzes the reaction of glutamine, tRNA(Gln), and ATP to form Gln-tRNA(Gln), AMP, and pyrophosphate. The enzyme is a class I tRNA synthetase. The same gene encodes both the cytosolic and mitochondrial QARS enzymes (Lamour et al. 1994).
Mitochondrial PPA2 (pyrophosphatase (inorganic) 2) catalyzes the hydrolysis of pyrophosphate to yield two molecules of orthophosphate. The enzyme requires Mg++ for activity (Curbo et al. 2006). The enzyme is inferred to be a homodimer by analogy to its cytosolic isoform.
Cytosolic PPA1 (pyrophosphatase (inorganic) 1) catalyzes the hydrolysis of pyrophosphate to yield two molecules of orthophosphate. The enzyme, a homodimer, requires Mg++ for activity (Fisher et al. 1974; Pynes and Younathan 1967; Thuiller et al. 1978).
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multienzyme complexAnnotated Interactions
synthetase
multienzyme complexsynthetase
multienzyme complexsynthetase
multienzyme complexsynthetase
multienzyme complexsynthetase
multienzyme complexsynthetase
multienzyme complexsynthetase
multienzyme complexsynthetase
multienzyme complexsynthetase
multienzyme complex