グリシンtRNAリガーゼ

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glycine-tRNA ligase
識別子
EC番号	6.1.1.14
CAS登録番号	9037-62-1
データベース
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB構造	RCSB PDB PDBj PDBe PDBsum
遺伝子オントロジー	AmiGO / QuickGO
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	テンプレートを表示

グリシンtRNAリガーゼ(Glycine—tRNA ligase、EC 6.1.1.14)は、酵素である。ヒトでは、GARS遺伝子によってコードされる^[1]^[2]^[3]。この酵素はリガーゼに分類され、特にアミノアシルtRNAと関連化合物に炭素-酸素結合を形成する。系統名はグリシン:tRNAGlyリガーゼ(AMP生成)(Glycine:tRNAGly ligase (AMP-forming))である。グリシルtRNAシンテターゼ(Glycyl-tRNA synthetase)、グリシルトランスラーゼ(Glycyl translase)等とも呼ばれる。

機能[編集]

グリシンtRNAリガーゼは、tRNAを関連するアミノ酸と結合させるアミノアシルtRNA合成酵素の一種である。酵素はα²二量体を形成し、II型のtRNA合成酵素である^[3]。

反応[編集]

グリシンtRNAリガーゼは、以下の化学反応を触媒する酵素である。

ATP + グリシン + tRNAGly

\rightleftharpoons

AMP + 二リン酸 + グリシルtRNAGly

従って、この酵素は、ATPとグリシンとtRNAGlyの3つの基質、AMPと二リン酸とグリシルtRNAGlyの3つの生成物を持つ。

この酵素は、グリシン、セリン、トレオニンの代謝、アミノアシルtRNAの生合成に関与する。

相互作用[編集]

グリシンtRNAリガーゼは、EEF1Dとタンパク質間相互作用することが示されている^[4]。

臨床的関連[編集]

この酵素は、多発性筋炎、皮膚筋炎等のヒト自己免疫疾患の自己抗原のターゲットとなっていることが示されている^[3]。

出典[編集]

^ Nichols RC, Pai SI, Ge Q, Targoff IN, Plotz PH, Liu P (Apr 1996). “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. doi:10.1006/geno.1995.0028. PMID 8595897.
^ Ionasescu V, Searby C, Sheffield VC, Roklina T, Nishimura D, Ionasescu R (Jan 1997). “Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D)”. Hum Mol Genet 5 (9): 1373–5. doi:10.1093/hmg/5.9.1373. PMID 8872480.
^ ^a ^b ^c “Entrez Gene: GARS glycyl-tRNA synthetase”. 2013年3月23日閲覧。
^ Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S (February 2002). “Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex”. Biochem. Biophys. Res. Commun. 291 (1): 158–64. doi:10.1006/bbrc.2002.6398. PMID 11829477.

関連文献[編集]

FRASER MJ (1963). “Glycyl-RNA synthetase of rat liver: partial purification and effects of some metal ions on its activity”. Can. J. Biochem. Physiol. 41: 1123–33. PMID 13959340.
Niyomporn B, Dahl JL, Strominger JL (1968). “Biosynthesis of the peptidoglycan of bacterial cell walls. IX Purification and properties of glycyl transfer ribonucleic acid synthetase from Staphylococcus aureus”. J. Biol. Chem. 243 (4): 773–8. PMID 4295604.
Hipps D, Shiba K, Henderson B, Schimmel P (1995). “Operational RNA code for amino acids: species-specific aminoacylation of minihelices switched by a single nucleotide.”. Proc. Natl. Acad. Sci. U.S.A. 92 (12): 5550–2. doi:10.1073/pnas.92.12.5550. PMC 41733. PMID 7539919.
Williams J, Osvath S, Khong TF, et al. (1995). “Cloning, sequencing and bacterial expression of human glycine tRNA synthetase.”. Nucleic Acids Res. 23 (8): 1307–10. doi:10.1093/nar/23.8.1307. PMC 306854. PMID 7753621.
Ge Q, Trieu EP, Targoff IN (1994). “Primary structure and functional expression of human Glycyl-tRNA synthetase, an autoantigen in myositis.”. J. Biol. Chem. 269 (46): 28790–7. PMID 7961834.
Shiba K, Schimmel P, Motegi H, Noda T (1994). “Human glycyl-tRNA synthetase. Wide divergence of primary structure from bacterial counterpart and species-specific aminoacylation.”. J. Biol. Chem. 269 (47): 30049–55. PMID 7962006.
Rho SB, Lee KH, Kim JW, et al. (1996). “Interaction between human tRNA synthetases involves repeated sequence elements.”. Proc. Natl. Acad. Sci. U.S.A. 93 (19): 10128–33. doi:10.1073/pnas.93.19.10128. PMC 38348. PMID 8816763.
Mudge SJ, Williams JH, Eyre HJ, et al. (1998). “Complex organisation of the 5'-end of the human glycine tRNA synthetase gene.”. Gene 209 (1-2): 45–50. doi:10.1016/S0378-1119(98)00007-9. PMID 9524218.
Kneussel M, Hermann A, Kirsch J, Betz H (1999). “Hydrophobic interactions mediate binding of the glycine receptor beta-subunit to gephyrin.”. J. Neurochem. 72 (3): 1323–6. doi:10.1046/j.1471-4159.1999.0721323.x. PMID 10037506.
Sang Lee J, Gyu Park S, Park H, et al. (2002). “Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex.”. Biochem. Biophys. Res. Commun. 291 (1): 158–64. doi:10.1006/bbrc.2002.6398. PMID 11829477.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). “Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.”. Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Scherer SW, Cheung J, MacDonald JR, et al. (2003). “Human chromosome 7: DNA sequence and biology.”. Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205.
Antonellis A, Ellsworth RE, Sambuughin N, et al. (2003). “Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V.”. Am. J. Hum. Genet. 72 (5): 1293–9. doi:10.1086/375039. PMC 1180282. PMID 12690580.
Hillier LW, Fulton RS, Fulton LA, et al. (2003). “The DNA sequence of human chromosome 7.”. Nature 424 (6945): 157–64. doi:10.1038/nature01782. PMID 12853948.
Gerhard DS, Wagner L, Feingold EA, et al. (2004). “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”. Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
Del Bo R, Locatelli F, Corti S, et al. (2006). “Coexistence of CMT-2D and distal SMA-V phenotypes in an Italian family with a GARS gene mutation.”. Neurology 66 (5): 752–4. doi:10.1212/01.wnl.0000201275.18875.ac. PMID 16534118.
James PA, Cader MZ, Muntoni F, et al. (2006). “Severe childhood SMA and axonal CMT due to anticodon binding domain mutations in the GARS gene.”. Neurology 67 (9): 1710–2. doi:10.1212/01.wnl.0000242619.52335.bc. PMID 17101916.
Xie W, Schimmel P, Yang XL (2006). “Crystallization and preliminary X-ray analysis of a native human tRNA synthetase whose allelic variants are associated with Charcot-Marie-Tooth disease.”. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 62 (Pt 12): 1243–6. doi:10.1107/S1744309106046434. PMC 2225372. PMID 17142907.
Cader MZ, Ren J, James PA, et al. (2007). “Crystal structure of human wildtype and S581L-mutant glycyl-tRNA synthetase, an enzyme underlying distal spinal muscular atrophy.”. FEBS Lett. 581 (16): 2959–64. doi:10.1016/j.febslet.2007.05.046. PMID 17544401.
Xie W, Nangle LA, Zhang W, et al. (2007). “Long-range structural effects of a Charcot-Marie-Tooth disease-causing mutation in human glycyl-tRNA synthetase.”. Proc. Natl. Acad. Sci. U.S.A. 104 (24): 9976–81. doi:10.1073/pnas.0703908104. PMC 1891255. PMID 17545306.

外部リンク[編集]

[pmid8595897-1] Nichols RC, Pai SI, Ge Q, Targoff IN, Plotz PH, Liu P (Apr 1996). “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. doi:10.1006/geno.1995.0028. PMID 8595897.

[pmid8872480-2] Ionasescu V, Searby C, Sheffield VC, Roklina T, Nishimura D, Ionasescu R (Jan 1997). “Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D)”. Hum Mol Genet 5 (9): 1373–5. doi:10.1093/hmg/5.9.1373. PMID 8872480.

[entrez-3] “Entrez Gene: GARS glycyl-tRNA synthetase”. 2013年3月23日閲覧。

[pmid11829477-4] Sang Lee J, Gyu Park S, Park H, Seol W, Lee S, Kim S (February 2002). “Interaction network of human aminoacyl-tRNA synthetases and subunits of elongation factor 1 complex”. Biochem. Biophys. Res. Commun. 291 (1): 158–64. doi:10.1006/bbrc.2002.6398. PMID 11829477.

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