Seryl-tRNA synthetase

The formation of 0-seryl or 0-prolyl esters (Figure 1) of certain N-hydroxy arylamines has been inferred from the observations that highly reactive intermediates can be generated in vitro by incubation with ATP, serine or proline, and the corresponding aminoacyl tRNA synthetases (11,12,119). For example, activation of N-hydroxy-4-aminoquinoline-l-oxide (119,120), N-hydroxy-4-aminoazobenzene (11) and N-hydroxy-Trp-P-2 (121) to nucleic acid-bound products was demonstrated using seryl-tRNA synthetase from yeast or rat ascites hepatoma cells. More recently, hepatic cytosolic prolyl-, but not seryl-, tRNA synthetase was shown to activate N-hydroxy-Trp-P-2 (12) however, no activation was detectable for the N-hydroxy metabolites of AF, 3,2 -dimethyl-4-aminobiphenyl, or N -acetylbenzidine (122). 

Biou, V., Yaremchuk, A., Tukalo, M., and Cusack, S. (1994). The 2.9 A crystal structure of T. thermophilus seryl-tRNA synthetase complexed with tRNA(Ser). Science 263, 1404-1410. 

The product of the selC gene, tRNA =, was identified as a novel tRNA species. Its structure differs from the features of all elongator tRNAs. With 95 nucleotides, it is the longest tRNA known to date. It has a variable loop of 22 nucleotides, an eight-base-pair aminoacyl acceptor stem, and a number of deviations from tRNA consensus structure. tRNA is charged with L-serine by the cellular seryl-tRNA synthetase, which is responsible for aminoacylation of the serine isoacceptor species. Thus, selenocysteine is formed from a serine residue charged to tRNA =. 

Figure 5 Structural features of the tRNA from E. coli. Elements involved in recognition by seryl-tRNA synthetase are shaded, antideterminants against recognition by EF-Tu are hatched. The modified bases are D dihydrouridine F pseudouridine i A isopentenyl-adenosine T ribothymidine. Tertiary interactions involving base pairing are indicated by lines, those with intercalations by arrows...

Several aaRS-like proteins are involved in metabobc pathways (1). For example, E. coli asparagine synthase, an aspartyl-tRNA synthetase (AspRS)-like enzyme, catalyzes the synthesis of asparagine from aspartate and ATP. A paralog of LysRS-II, called PoxA/GenX, is important for pyruvate oxidase activity in E. coli and Salmonella typhimurium and for virulence in S. typhimurium. The E. coli biotin synthetase/repressor protein (BirA), which has a domain that resembles structurally the seryl-tRNA synthetase (SerRS) catalytic domain, activates biotin to modify posttranslationaUy various metabolic proteins involved in carboxylation and decarboxylation. BirA can also bind DNA and regulate its own transcription using biotin as a corepressor. A histidyl-tRNA synthetase (HisRS)-hke protein from Lactococcus lactis, HisZ is involved in the allosteric activation of the phosphoribosyl-transferase reaction. 

R. A second class of synthetase structure revealed by X-ray analysis of Escherichia coli seryl-tRNA synthetase at 2.5 A. Nature 1990 347 249-255. 

In bacteria, seryl-tRNA synthetase initiates selenocysteine biosynthesis by charging tRNA with serine. The aminoacy-lation efficiency of this reaction is only 1-10% that of aminoa-cylation of tRNA " (44). In E. coli, selenocysteine synthase, encoded by selA, catalyzes the conversion to seryl-tRNA to selenocysteyl-tRNA (45). Seryl-tRNA covalently binds to the pyridoxal phosphate (PUP) of selenocysteine synthase. From in vitro studies, after the elimination of a water molecule from the seryl moiety, formal addition of hydrogen selenide to... 

In archaea (42) and eukarya (48), selenocysteine also starts with the serylation of tRNA by seryl-tRNA synthetase. In the presence of Mg + and ATP, phosphoseryl-tRNA kinase specifically phosphorylates the seryl moiety of Ser-tRNA to produce 0-phosphoseryl-tRNA (49). The conversion of 0-phosphoserine (Sep) to selenocysteine proceeds by the action of the PFP-dependent enzyme Sep-tRNA Sec-tRNA synthase (SepSecS) using selenophosphate as a selenium donor to produce Sec-tRNA (50). As the phosphate of Sep provides a better leaving group than the water of serine, Sep to Sec conversion is more chemically favorable than Ser to Sec conversion. This favorableness and the greater stability of the Sep-tRNA as compared with Ser-tRNA (49) would enhance the production of Sec-tRNA in archaea and eukarya, which have more extended selenoproteomes than bacteria (50). 

Bilokapic S, Korencic D, Soil D, Weygand-Durasevic I. The 66. unusual methanogenic seryl-tRNA synthetase recognizes tRNASer species from all three kingdoms of life. Eur. J. Biochem. 2004 271 694-702. 

Finally, we briefly consider the way in which Sec is generated and co-translationally incorporated in selenoproteins. There are 25 selenoprotein genes in humans, and Sec has been found in the active site of those to which a function has been attributed. Sec does not occur as the free amino acid, and the biosynthetic pathway of Sec from serine on tRNA in eukaryotes requires four enzymes, as illustrated in Figure 18.8. The specific tRNA is aminoacylated with serine by the conventional Seryl-tRNA synthetase (SerRS) and the... 

Belrhali H, Yaremchuk A, Tukalo M, Berthet-Colominas C, Rasmussen B, Bosecke P, Diat O, Cusack S The structural basis for seryl-adenylate and Ap4A synthesis by seryl-tRNA synthetase. Structure 1995, 3(4) 341—352. 

Bilokapic S, Maier T, Ahel D, Gruic-Sovulj I, Soil D, Weygand-Durasevic I, Ban N Structure of the unusual seryl-tRNA synthetase reveals a distinct zinc-dependent mode of substrate recognition. EMBO J 2006, 25(11) 2498—2509. 

The protein YT320 was prepared by tandem polymerisation of the 42-bp long microgene, MG-15, whose first coding frame had similarity to a segment of the coiled coil a-helix of the natural protein (seryl-tRNA synthetase). The... 

Insertion of selenocysteine requires several adaptations of the translational machinery. First, tRNA is aminoacylated with serine by seryl-tRNA synthetase. The serine attached to this misacylated species is then converted... 

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