From one amino acid to another: tRNA-dependent amino acid biosynthesis - PubMed (original) (raw)

Review

. 2008 Apr;36(6):1813-25.

doi: 10.1093/nar/gkn015. Epub 2008 Feb 5.

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Review

From one amino acid to another: tRNA-dependent amino acid biosynthesis

Kelly Sheppard et al. Nucleic Acids Res. 2008 Apr.

Abstract

Aminoacyl-tRNAs (aa-tRNAs) are the essential substrates for translation. Most aa-tRNAs are formed by direct aminoacylation of tRNA catalyzed by aminoacyl-tRNA synthetases. However, a smaller number of aa-tRNAs (Asn-tRNA, Gln-tRNA, Cys-tRNA and Sec-tRNA) are made by synthesizing the amino acid on the tRNA by first attaching a non-cognate amino acid to the tRNA, which is then converted to the cognate one catalyzed by tRNA-dependent modifying enzymes. Asn-tRNA or Gln-tRNA formation in most prokaryotes requires amidation of Asp-tRNA or Glu-tRNA by amidotransferases that couple an amidase or an asparaginase to liberate ammonia with a tRNA-dependent kinase. Both archaeal and eukaryotic Sec-tRNA biosynthesis and Cys-tRNA synthesis in methanogens require O-phosophoseryl-tRNA formation. For tRNA-dependent Cys biosynthesis, O-phosphoseryl-tRNA synthetase directly attaches the amino acid to the tRNA which is then converted to Cys by Sep-tRNA: Cys-tRNA synthase. In Sec-tRNA synthesis, O-phosphoseryl-tRNA kinase phosphorylates Ser-tRNA to form the intermediate which is then modified to Sec-tRNA by Sep-tRNA:Sec-tRNA synthase. Complex formation between enzymes in the same pathway may protect the fidelity of protein synthesis. How these tRNA-dependent amino acid biosynthetic routes are integrated into overall metabolism may explain why they are still retained in so many organisms.

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Figures

Figure 1.

Figure 1.

Indirect pathways for (A) Gln-tRNAGln and (B) Asn-tRNAAsn formation. (A) First a ND-GluRS glutamylates tRNAGln to form Glu-tRNAGln. The mischarged species is then amidated by a Glu-AdT to form Gln-tRNAGln. (B) First a ND-AspRS aspartylates tRNAAsn to form Asp-tRNAAsn. The mischarged species is then amidated by an Asp-AdT for form Asn-tRNAAsn.

Figure 2.

Figure 2.

Crystal structure of the M. thermautotrophicus GatDE complexed with tRNAGln. The AdT forms an α2β2 tetramer, with two GatE subunits binding a GatD homodimer. Each GatE subunit binds one tRNAGln molecule. For clarity only one monomer of GatD and GatE are shown. The glutaminase active site of the D-subunit and the kinase active site of the E-subunit are connected by a 40 Å long molecular tunnel (44). Adapted from Polycarpo,C. et al. (2007). In Cavicchioli,R. (ed.) Archaea: Molecular and Cellular Biology. ASM Press, Washington, DC USA with permission from ASM Press.

Figure 3.

Figure 3.

Both GatCAB (A and B) and GatDE (A) catalyze three distinct reactions in order to transamidate their mischarged tRNA species, (A) Glu-tRNAGln and/or (B) Asp-tRNAAsn: (i) the kinase subunit of the respective AdT (GatB or GatE) phosphorylates the mischarged tRNA species to form an activated intermediate, (A) γ-phosphoryl-Glu-tRNAGln or (B) β-phosphoryl-Asp-tRNAAsn; (ii) the glutaminase subunit (GatA or GatD) hydrolyzes an amide donor such as Gln or Asn to release ammonia. A molecular tunnel connects the glutaminase and kinase active sites of the respective AdTs, allowing ammonia liberated from the glutamianse subunit (GatA or GatD) to flow to the kinase subunit (GatB or GatE) (denoted by the dashed arrow); (iii) the liberated ammonia is then used by the kinase subunit (GatB or GatE) to amidate the activated intermediate to form the product aa-tRNA, (A) Gln-tRNAGln or (B) Asn-tRNAAsn.

Figure 4.

Figure 4.

Indirect pathway for Cys-tRNACys formation. First, SepRS aminoacylates tRNACys with Sep to form Sep-tRNACys. The Sep bound to the tRNA is then converted to Cys by SepCysS in the presence of a sulfur donor to form Cys-tRNACys.

Figure 5.

Figure 5.

The crystal structures of the active sites of A. fulgidus SepCysS and M. maripaludis SepSecS. In both, the different monomers of the respective enzyme are colored pink and blue. PLP and residues in the catalytic centers are shown as ball-and-stick models (adapted from 136).

Figure 6.

Figure 6.

Indirect pathways for Sec-tRNASec formation. In all known Sec-decoding organisms, first SerRS aminoacylates tRNASec with Ser to form Ser-tRNASec. In Sec-decoding bacteria, the Ser bound to the tRNA is directly converted to Sec in the presence of selenophosphate by SelA to form Sec-tRNASec. In Sec-decoding eukaryotes and Archaea, the Ser-moiety on tRNASec is first phosphorylated by PSTK to form Sep-tRNASec. The Sep bound to the tRNA is then converted to Sec in the presence of selenophosphate by SepSecS to form Sec-tRNASec.

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