Biology:Glycine—tRNA ligase
Glycine—tRNA ligase | |||||||||
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Identifiers | |||||||||
EC number | 6.1.1.14 | ||||||||
CAS number | 9037-62-1 | ||||||||
Databases | |||||||||
IntEnz | IntEnz view | ||||||||
BRENDA | BRENDA entry | ||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
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Generic protein structure example |
Glycine—tRNA ligase also known as glycyl–tRNA synthetase is an enzyme that in humans is encoded by the GARS1 gene.[1][2][3]
Function
This gene encodes glycyl-tRNA synthetase, one of the aminoacyl-tRNA synthetases that charge tRNAs with their cognate amino acids. The encoded enzyme is an (alpha)2 dimer which belongs to the class II family of tRNA synthetases.[3]
Reaction
In enzymology, a glycine—tRNA ligase (EC 6.1.1.14) is an enzyme that catalyzes the chemical reaction
- ATP + glycine + tRNAGly [math]\displaystyle{ \rightleftharpoons }[/math] AMP + diphosphate + glycyl-tRNAGly
The 3 substrates of this enzyme are ATP, glycine, and tRNA(Gly), whereas its 3 products are AMP, diphosphate, and glycyl-tRNA(Gly).
This enzyme belongs to the family of ligases, to be specific those forming carbon-oxygen bonds in aminoacyl-tRNA and related compounds. The systematic name of this enzyme class is glycine:tRNAGly ligase (AMP-forming). Other names in common use include glycyl-tRNA synthetase, glycyl-transfer ribonucleate synthetase, glycyl-transfer RNA synthetase, glycyl-transfer ribonucleic acid synthetase, and glycyl translase. This enzyme participates in glycine, serine and threonine metabolism and aminoacyl-trna biosynthesis.
Interactions
Glycyl-tRNA synthetase has been shown to interact with EEF1D.[4] Mutant forms of the protein associated with peripheral nerve disease have been shown to aberrantly bind to the transmembrane receptor proteins neuropilin 1[5] and Trk receptors A-C.[6]
Clinical relevance
Glycyl-tRNA synthetase has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis.[3]
The peripheral nerve diseases Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V) have been liked to dominant mutations in GARS.[7][8] CMT2D usually manifests during the teenage years, and results in muscle weakness predominantly in the hands and feet.[9] Two mouse models of CMT2D have been used to better understand the disease, identifying that the disorder is caused by a toxic gain-of-function of the mutant glycine-tRNA ligase protein.[10] The CMT2D mice display peripheral nerve axon degeneration [11][12] and defective development[13] and function[14]> of the neuromuscular junction.
References
- ↑ "Localization of two human autoantigen genes by PCR screening and in situ hybridization--glycyl-tRNA synthetase locates to 7p15 and alanyl-tRNA synthetase locates to 16q22". Genomics 30 (1): 131–2. Nov 1995. doi:10.1006/geno.1995.0028. PMID 8595897. https://zenodo.org/record/1229644.
- ↑ "Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D)". Human Molecular Genetics 5 (9): 1373–5. Sep 1996. doi:10.1093/hmg/5.9.1373. PMID 8872480.
- ↑ 3.0 3.1 3.2 "Entrez Gene: GARS glycyl-tRNA synthetase". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2617.
- ↑ "Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex". Biochemical and Biophysical Research Communications 291 (1): 158–64. Feb 2002. doi:10.1006/bbrc.2002.6398. PMID 11829477.
- ↑ "CMT2D neuropathy is linked to the neomorphic binding activity of glycyl-tRNA synthetase". Nature 526 (7575): 710–4. 2015. doi:10.1038/nature15510. PMID 26503042. Bibcode: 2015Natur.526..710H.
- ↑ "Trk receptor signaling and sensory neuron fate are perturbed in human neuropathy caused by Gars mutations". Proc Natl Acad Sci U S A 114 (16): E3324–E3333. 2017. doi:10.1073/pnas.1614557114. PMID 28351971. Bibcode: 2017PNAS..114E3324S.
- ↑ "GARS axonopathy: not every neuron's cup of tRNA". Trends in Neurosciences 33 (2): 59–66. Feb 2010. doi:10.1016/j.tins.2009.11.001. PMID 20152552.
- ↑ "Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V". American Journal of Human Genetics 72 (5): 1293–9. 2003. doi:10.1086/375039. PMID 12690580.
- ↑ "Phenotypic spectrum of disorders associated with glycyl-tRNA synthetase mutations". Brain 128 (Pt 10): 2304–14. Oct 2005. doi:10.1093/brain/awh590. PMID 16014653.
- ↑ "Charcot-Marie-Tooth-linked mutant GARS is toxic to peripheral neurons independent of wild-type GARS levels". PLOS Genetics 7 (12): e1002399. Dec 2011. doi:10.1371/journal.pgen.1002399. PMID 22144914.
- ↑ "An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model". Neuron 51 (6): 715–26. Sep 2006. doi:10.1016/j.neuron.2006.08.027. PMID 16982418.
- ↑ "An ENU-induced mutation in mouse glycyl-tRNA synthetase (GARS) causes peripheral sensory and motor phenotypes creating a model of Charcot-Marie-Tooth type 2D peripheral neuropathy". Disease Models & Mechanisms 2 (7–8): 359–73. Jul–Aug 2009. doi:10.1242/dmm.002527. PMID 19470612.
- ↑ "Neuromuscular junction maturation defects precede impaired lower motor neuron connectivity in Charcot-Marie-Tooth type 2D mice". Human Molecular Genetics 23 (10): 2639–50. May 2014. doi:10.1093/hmg/ddt659. PMID 24368416.
- ↑ "Synaptic Deficits at Neuromuscular Junctions in Two Mouse Models of Charcot-Marie-Tooth Type 2d". The Journal of Neuroscience 36 (11): 3254–67. 2016. doi:10.1523/JNEUROSCI.1762-15.2016. PMID 26985035.
Further reading
- "Glycyl-RNA synthetase of rat liver: partial purification and effects of some metal ions on its activity". Canadian Journal of Biochemistry and Physiology 41 (5): 1123–33. May 1963. doi:10.1139/o63-128. PMID 13959340.
- "Biosynthesis of the peptidoglycan of bacterial cell walls. IX. Purification and properties of glycyl transfer ribonucleic acid synthetase from Staphylococcus aureus". The Journal of Biological Chemistry 243 (4): 773–8. Feb 1968. doi:10.1016/S0021-9258(19)81732-5. PMID 4295604.
- "Operational RNA code for amino acids: species-specific aminoacylation of minihelices switched by a single nucleotide". Proceedings of the National Academy of Sciences of the United States of America 92 (12): 5550–2. Jun 1995. doi:10.1073/pnas.92.12.5550. PMID 7539919. Bibcode: 1995PNAS...92.5550H.
- "Cloning, sequencing and bacterial expression of human glycine tRNA synthetase". Nucleic Acids Research 23 (8): 1307–10. Apr 1995. doi:10.1093/nar/23.8.1307. PMID 7753621.
- "Primary structure and functional expression of human Glycyl-tRNA synthetase, an autoantigen in myositis". The Journal of Biological Chemistry 269 (46): 28790–7. Nov 1994. doi:10.1016/S0021-9258(19)61975-7. PMID 7961834.
- "Human glycyl-tRNA synthetase. Wide divergence of primary structure from bacterial counterpart and species-specific aminoacylation". The Journal of Biological Chemistry 269 (47): 30049–55. Nov 1994. doi:10.1016/S0021-9258(18)43986-5. PMID 7962006.
- "Interaction between human tRNA synthetases involves repeated sequence elements". Proceedings of the National Academy of Sciences of the United States of America 93 (19): 10128–33. Sep 1996. doi:10.1073/pnas.93.19.10128. PMID 8816763. Bibcode: 1996PNAS...9310128R.
- "Complex organisation of the 5'-end of the human glycine tRNA synthetase gene". Gene 209 (1–2): 45–50. Mar 1998. doi:10.1016/S0378-1119(98)00007-9. PMID 9524218.
- "Hydrophobic interactions mediate binding of the glycine receptor beta-subunit to gephyrin". Journal of Neurochemistry 72 (3): 1323–6. Mar 1999. doi:10.1046/j.1471-4159.1999.0721323.x. PMID 10037506.
- "Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex". Biochemical and Biophysical Research Communications 291 (1): 158–64. Feb 2002. doi:10.1006/bbrc.2002.6398. PMID 11829477.
- "Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V". American Journal of Human Genetics 72 (5): 1293–9. May 2003. doi:10.1086/375039. PMID 12690580.
- "Coexistence of CMT-2D and distal SMA-V phenotypes in an Italian family with a GARS gene mutation". Neurology 66 (5): 752–4. Mar 2006. doi:10.1212/01.wnl.0000201275.18875.ac. PMID 16534118.
- "Severe childhood SMA and axonal CMT due to anticodon binding domain mutations in the GARS gene". Neurology 67 (9): 1710–2. Nov 2006. doi:10.1212/01.wnl.0000242619.52335.bc. PMID 17101916.
- "Crystallization and preliminary X-ray analysis of a native human tRNA synthetase whose allelic variants are associated with Charcot-Marie-Tooth disease". Acta Crystallographica Section F 62 (Pt 12): 1243–6. Dec 2006. doi:10.1107/S1744309106046434. PMID 17142907.
- "Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an enzyme underlying distal spinal muscular atrophy". FEBS Letters 581 (16): 2959–64. Jun 2007. doi:10.1016/j.febslet.2007.05.046. PMID 17544401.
- "Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase". Proceedings of the National Academy of Sciences of the United States of America 104 (24): 9976–81. Jun 2007. doi:10.1073/pnas.0703908104. PMID 17545306. Bibcode: 2007PNAS..104.9976X.
External links
- GeneReviews/NCBI/NIH/UW entry on Charcot-Marie-Tooth Neuropathy Type 2
- GeneReviews/NCBI/NIH/UW entry on GARS-Associated Axonal Neuropathy, Charcot-Marie-Tooth Neuropathy Type 2D, Distal Spinal Muscular Atrophy V
Original source: https://en.wikipedia.org/wiki/Glycine—tRNA ligase.
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