YARS1: A Potential Drug Target and Biomarker for Tyrosyl-TRNA Synthesis

Target Name: YARS1

NCBI ID: G8565

YARS1

YARS1: A Potential Drug Target and Biomarker for Tyrosyl-TRNA Synthesis

Introduction

Tyrosyl-tRNA synthetase (YARS1) is a key enzyme in the regulation of protein synthesis in eukaryotic cells. It catalyzes the conversion of tryptophan (Phe) to tyrosyl-tRNA (TTR) via a post-translational modification, which is critical for the accurate reading of protein sequences and for the production of functional proteins. The regulation of YARS1 activity is essential for the proper cell function, and dysregulation of YARS1 has been implicated in a variety of diseases, including cancer, neurodegenerative diseases, and autoimmune disorders.

As a result, targeting YARS1 has emerged as a promising strategy for the development of new therapeutic approaches. Several small molecules have been shown to inhibit YARS1 activity, and these compounds have been tested in a variety of cellular and animal models as potential drug targets. In this article, we will focus on YARS1 as a drug target and biomarker, highlighting its significance for the development of new treatments and the understanding of its underlying mechanisms.

YARS1: Structure, Functions, and Interactions

YARS1 is a 26 kDa protein that belongs to the nucleotide transporter family 1 (Ntpr). It was first identified in 1995 and has been shown to have critical functions in various cellular processes, including protein synthesis, cell signaling, and cell survival. YARS1 is primarily localized to the cytoplasm and is involved in the delivery of essential amino acids to the cytoplasm, as well as the removal of synthesized proteins to the endoplasmic reticulum (ER).

YARS1 is composed of a unique nucleotide-binding domain (NBD), a catalytic domain, and a cytoplasmic region. The NBD is responsible for the binding of small molecules, including inhibitors, to the active site of the enzyme. The catalytic domain is responsible for the catalytic activity of YARS1, while the cytoplasmic region is involved in the regulation of YARS1 activity.

YARS1 has multiple interactions with other cellular components, including other proteins and nucleic acids. It has been shown to interact with novobiocin A1, a potent inhibitor of YARS1 activity, as well as with various tRNA species, including tryptophan tRNA. In addition, YARS1 has been shown to interact with the protein hsp70, which is involved in the regulation of YARS1 activity.

YARS1 as a Drug Target

Several small molecules have been shown to inhibit the activity of YARS1, and these compounds have been tested in a variety of cellular and animal models as potential drug targets. One of the most promising compounds is N-[2-(4-fluorophenyl)- 10-(2-methylpropyl)-amino]-1-(3-isothiocyanatopyrrolidin-1-yl)-propanethiol (FAP-1), which is a potent inhibitor of YARS1 activity.

FAP-1 works by binding to the NBD of YARS1 and inhibiting the binding of small molecules to the active site. This inhibition results in the inability of YARS1 to catalyze the conversion of tryptophan to tyrosyl-tRNA, thereby inhibiting protein synthesis. In addition, FAP-1 has been shown to induce apoptosis (9) in YARS1-expressing cells, suggesting that it may have an additional role in the regulation of cellular processes, including cell death.

Another promising compound is N-[2-(4-fluorophenyl)-10-(2-methylpropyl)-amino]-1-(3

Protein Name: Tyrosyl-tRNA Synthetase 1

Functions: Tyrosine--tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr) (Probable) (PubMed:25533949). Also acts as a positive regulator of poly-ADP-ribosylation in the nucleus, independently of its tyrosine--tRNA ligase activity (PubMed:25533949). Activity is switched upon resveratrol-binding: resveratrol strongly inhibits the tyrosine--tRNA ligase activity and promotes relocalization to the nucleus, where YARS1 specifically stimulates the poly-ADP-ribosyltransferase activity of PARP1 (PubMed:25533949)

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•   expression level;
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The report is helpful for project application, drug molecule design, research progress updates, publication of research papers, patent applications, etc. If you are interested to get a full version of this report, please feel free to contact us at BD@silexon.ai

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