Structural Basis of Furan-Amino Acid Recognition by a Polyspecific Aminoacyl-tRNA-Synthetase and its Genetic Encoding in Human Cells

ChemBioChem ◽  
2014 ◽  
Vol 15 (12) ◽  
pp. 1755-1760 ◽  
Author(s):  
Moritz J. Schmidt ◽  
Annemarie Weber ◽  
Moritz Pott ◽  
Wolfram Welte ◽  
Daniel Summerer
Keyword(s):  
Amino Acid ◽  
Trna Synthetase ◽  
Human Cells ◽  
Structural Basis ◽  
Aminoacyl Trna Synthetase ◽  
Genetic Encoding ◽  
Amino Acid Recognition

scholarly journals Transfer RNA-dependent cognate amino acid recognition by an aminoacyl-tRNA synthetase.

1996 ◽  
Vol 15 (8) ◽  
pp. 1983-1991 ◽  
Author(s):  
K. W. Hong ◽  
M. Ibba ◽  
I. Weygand-Durasevic ◽  
M. J. Rogers ◽  
H. U. Thomann ◽  
...  
Keyword(s):  
Amino Acid ◽  
Trna Synthetase ◽  
Transfer Rna ◽  
Aminoacyl Trna Synthetase ◽  
Amino Acid Recognition

Specific amino acid recognition by aspartyl-tRNA synthetase studied by free energy simulations 1 1A. R. Fersht

1998 ◽  
Vol 275 (5) ◽  
pp. 823-846 ◽  
Author(s):  
Georgios Archontis ◽  
Thomas Simonson ◽  
Dino Moras ◽  
Martin Karplus
Keyword(s):  
Free Energy ◽  
Amino Acid ◽  
Trna Synthetase ◽  
Specific Amino Acid ◽  
Energy Simulations ◽  
Amino Acid Recognition

How methionyl-tRNA synthetase creates its amino acid recognition pocket upon l-methionine binding

2001 ◽  
Vol 306 (4) ◽  
pp. 863-876 ◽  
Author(s):  
Laurence Serre ◽  
Grégory Verdon ◽  
Thomas Choinowski ◽  
Nadège Hervouet ◽  
Jean-Loup Risler ◽  
...  
Keyword(s):  
Amino Acid ◽  
Trna Synthetase ◽  
Methionyl Trna Synthetase ◽  
Amino Acid Recognition

scholarly journals Aminoacyl-tRNA synthetase inhibition activates a pathway that branches from the canonical amino acid response in mammalian cells

2020 ◽  
Vol 117 (16) ◽  
pp. 8900-8911 ◽  
Author(s):  
Yeonjin Kim ◽  
Mark S. Sundrud ◽  
Changqian Zhou ◽  
Maja Edenius ◽  
Davide Zocco ◽  
...  
Keyword(s):  
Amino Acid ◽  
Mammalian Cells ◽  
Inflammatory Responses ◽  
Mammalian Target Of Rapamycin ◽  
Cell Types ◽  
Trna Synthetase ◽  
Aminoacyl Trna Synthetase ◽  
Therapeutic Benefits ◽  
Fibroblast Like Synoviocytes ◽  
Amino Acid Response

Signaling pathways that sense amino acid abundance are integral to tissue homeostasis and cellular defense. Our laboratory has previously shown that halofuginone (HF) inhibits the prolyl-tRNA synthetase catalytic activity of glutamyl-prolyl-tRNA synthetase (EPRS), thereby activating the amino acid response (AAR). We now show that HF treatment selectively inhibits inflammatory responses in diverse cell types and that these therapeutic benefits occur in cells that lack GCN2, the signature effector of the AAR. Depletion of arginine, histidine, or lysine from cultured fibroblast-like synoviocytes recapitulates key aspects of HF treatment, without utilizing GCN2 or mammalian target of rapamycin complex 1 pathway signaling. Like HF, the threonyl-tRNA synthetase inhibitor borrelidin suppresses the induction of tissue remodeling and inflammatory mediators in cytokine-stimulated fibroblast-like synoviocytes without GCN2, but both aminoacyl-tRNA synthetase (aaRS) inhibitors are sensitive to the removal of GCN1. GCN1, an upstream component of the AAR pathway, binds to ribosomes and is required for GCN2 activation. These observations indicate that aaRS inhibitors, like HF, can modulate inflammatory response without the AAR/GCN2 signaling cassette, and that GCN1 has a role that is distinct from its activation of GCN2. We propose that GCN1 participates in a previously unrecognized amino acid sensor pathway that branches from the canonical AAR.

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