Crucial role of an idiosyncratic insertion in the Rossman fold of class 1 aminoacyl-tRNA synthetases: the case of methionyl-tRNA synthetase

Biochemistry ◽  
1995 ◽  
Vol 34 (48) ◽  
pp. 15681-15688 ◽  
Author(s):  
Dominique Fourmy ◽  
Yves Mechulam ◽  
Sylvain Blanquet
Keyword(s):  
Crucial Role ◽  
Trna Synthetase ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Class 1 ◽  
Methionyl Trna Synthetase

scholarly journals A Novel Aminoacyl-tRNA Synthetase Appended Domain Can Supply the Core Synthetase with Its Amino Acid Substrate

Genes ◽  
2020 ◽  
Vol 11 (11) ◽  
pp. 1320
Author(s):  
Marc Muraski ◽  
Emil Nilsson ◽  
Benjamin Weekley ◽  
Sandhya Bharti Sharma ◽  
Rebecca W. Alexander
Keyword(s):  
Trna Synthetase ◽  
Mycoplasma Species ◽  
Intracellular Pathogen ◽  
Aminoacyl Trna Synthetase ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Acid Analog ◽  
Methionyl Trna Synthetase ◽  
Acid Substrate ◽  
Amino Acid Substrate

The structural organization and functionality of aminoacyl-tRNA synthetases have been expanded through polypeptide additions to their core aminoacylation domain. We have identified a novel domain appended to the methionyl-tRNA synthetase (MetRS) of the intracellular pathogen Mycoplasma penetrans. Sequence analysis of this N-terminal region suggests the appended domain is an aminotransferase, which we demonstrate here. The aminotransferase domain of MpMetRS is capable of generating methionine from its α-keto acid analog, 2-keto-4-methylthiobutyrate (KMTB). The methionine thus produced can be subsequently attached to cognate tRNAMet in the MpMetRS aminoacylation domain. Genomic erosion in the Mycoplasma species has impaired many canonical biosynthetic pathways, causing them to rely on their host for numerous metabolites. It is still unclear if this bifunctional MetRS is a key part of pathogen life cycle or is a neutral consequence of the reductive evolution experienced by Mycoplasma species.

scholarly journals Nucleolar Localization of Human Methionyl–Trna Synthetase and Its Role in Ribosomal RNA Synthesis

2000 ◽  
Vol 149 (3) ◽  
pp. 567-574 ◽  
Author(s):  
Young-Gyu Ko ◽  
Young-Sun Kang ◽  
Eun-Kyoung Kim ◽  
Sang Gyu Park ◽  
Sunghoon Kim
Keyword(s):  
Protein Synthesis ◽  
Ribosomal Rna ◽  
Rna Synthesis ◽  
Trna Synthetase ◽  
Nucleolar Localization ◽  
Trna Synthetases ◽  
Quiescent Cells ◽  
Aminoacyl Trna Synthetases ◽  
Polymerase I ◽  
Methionyl Trna Synthetase

Human aminoacyl–tRNA synthetases (ARSs) are normally located in cytoplasm and are involved in protein synthesis. In the present work, we found that human methionyl–tRNA synthetase (MRS) was translocated to nucleolus in proliferative cells, but disappeared in quiescent cells. The nucleolar localization of MRS was triggered by various growth factors such as insulin, PDGF, and EGF. The presence of MRS in nucleoli depended on the integrity of RNA and the activity of RNA polymerase I in the nucleolus. The ribosomal RNA synthesis was specifically decreased by the treatment of anti-MRS antibody as determined by nuclear run-on assay and immunostaining with anti-Br antibody after incorporating Br-UTP into nascent RNA. Thus, human MRS plays a role in the biogenesis of rRNA in nucleoli, while it is catalytically involved in protein synthesis in cytoplasm.

scholarly journals Cloning and sequencing of cDNA encoding the rice methionyl-tRNA synthetase.

1998 ◽  
Vol 45 (3) ◽  
pp. 669-676 ◽  
Author(s):  
M Deniziak ◽  
M Mirande ◽  
J Barciszewski
Keyword(s):  
Trna Synthetase ◽  
Great Similarity ◽  
High Homology ◽  
Yeast Protein ◽  
Cloning And Sequencing ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
C Terminus ◽  
Signature Sequences ◽  
Methionyl Trna Synthetase

Three overlapping clones of cDNA, Mos43, Mos28 and Mos60, coding for methionyl-tRNA synthetase were obtained by screening the Oryza sativa lambda gt11 library. Their nucleotide sequence of 2850 bp was determined. The deduced amino-acid sequence of the isolated clones contains a HLGN and KFSKS motifs, which are conserved for this family of enzymes and have been proposed to be the signature sequences for class I aminoacyl-tRNA synthetases. A comparison of the rice MetRS primary structure with those deposited in EMBL/GenBank points to its high homology to yeast, human and Caenorhabditis elegans MetRSs. Interestingly, a great similarity of its C terminus to endothelial-monocyte-activating polypeptide II (EMAPII) and yeast protein G4p1 was observed.

scholarly journals Inhibitory mechanism of reveromycin A at the tRNA binding site of a class I synthetase

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Bingyi Chen ◽  
Siting Luo ◽  
Songxuan Zhang ◽  
Yingchen Ju ◽  
Qiong Gu ◽  
...  
Keyword(s):  
Binding Site ◽  
Catalytic Domain ◽  
Trna Synthetase ◽  
Rational Drug Design ◽  
Class I ◽  
Binding Assays ◽  
Trna Synthetases ◽  
Aminoacyl Trna Synthetases ◽  
Rational Drug ◽  
Trna Binding

AbstractThe polyketide natural product reveromycin A (RM-A) exhibits antifungal, anticancer, anti-bone metastasis, anti-periodontitis and anti-osteoporosis activities by selectively inhibiting eukaryotic cytoplasmic isoleucyl-tRNA synthetase (IleRS). Herein, a co-crystal structure suggests that the RM-A molecule occupies the substrate tRNAIle binding site of Saccharomyces cerevisiae IleRS (ScIleRS), by partially mimicking the binding of tRNAIle. RM-A binding is facilitated by the copurified intermediate product isoleucyl-adenylate (Ile-AMP). The binding assays confirm that RM-A competes with tRNAIle while binding synergistically with l-isoleucine or intermediate analogue Ile-AMS to the aminoacylation pocket of ScIleRS. This study highlights that the vast tRNA binding site of the Rossmann-fold catalytic domain of class I aminoacyl-tRNA synthetases could be targeted by a small molecule. This finding will inform future rational drug design.

scholarly journals Lysyl-tRNA synthetase from Escherichia coli K12. Chromatographic heterogeneity and the lysU-gene product

1987 ◽  
Vol 248 (1) ◽  
pp. 43-51 ◽  
Author(s):  
J Charlier ◽  
R Sanchez
Keyword(s):  
Escherichia Coli ◽  
Gene Product ◽  
Activity Ratio ◽  
Deae Cellulose ◽  
Trna Synthetase ◽  
Trna Synthetases ◽  
E Coli ◽  
Aminoacyl Trna Synthetases

In contrast with most aminoacyl-tRNA synthetases, the lysyl-tRNA synthetase of Escherichia coli is coded for by two genes, the normal lysS gene and the inducible lysU gene. During its purification from E. coli K12, lysyl-tRNA synthetase was monitored by its aminoacylation and adenosine(5′)tetraphospho(5′)adenosine (Ap4A) synthesis activities. Ap4A synthesis was measured by a new assay using DEAE-cellulose filters. The heterogeneity of lysyl-tRNA synthetase (LysRS) was revealed on hydroxyapatite; we focused on the first peak, LysRS1, because of its higher Ap4A/lysyl-tRNA activity ratio at that stage. Additional differences between LysRS1 and LysRS2 (major peak on hydroxyapatite) were collected. LysRS1 was eluted from phosphocellulose in the presence of the substrates, whereas LysRS2 was not. Phosphocellulose chromatography was used to show the increase of LysRS1 in cells submitted to heat shock. Also, the Mg2+ optimum in the Ap4A-synthesis reaction is much higher for LysRS1. LysRS1 showed a higher thermostability, which was specifically enhanced by Zn2+. These results in vivo and in vitro strongly suggest that LysRS1 is the heat-inducible lysU-gene product.

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