ArticleJournal of molecular biology2011
The double-length tyrosyl-tRNA synthetase from the eukaryote Leishmania major forms an intrinsically asymmetric pseudo-dimer.
Article in Journal of molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- AARS Online: A collaborative database on the structure, function, and evolution of the aminoacyl-tRNA synthetases.IUBMB life · 2024Article
- Aminoacyl tRNA Synthetases: Implications of Structural Biology in Drug Development against Trypanosomatid Parasites.ACS omega · 2023Review
- Diversification of aminoacyl-tRNA synthetase activitiesFrontiers in physiology · 2022Review
- Peculiarities of aminoacyl-tRNA synthetases from trypanosomatids.The Journal of biological chemistry · 2021Article
- Article
- Targeting tRNA-synthetase interactions towards novel therapeutic discovery against eukaryotic pathogens.PLoS neglected tropical diseases · 2020Article
- Drugging tRNA aminoacylation.RNA biology · 2018Review
- New molecular insights into the tyrosyl-tRNA synthase inhibitors: CoMFA, CoMSIA analyses and molecular docking studies.Scientific reports · 2017Article
- Article
- Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms.Scientific reports · 2017Article
- Bioinformatic Analysis Reveals Archaeal tRNALife (Basel, Switzerland) · 2017Article
- The Potential of Secondary Metabolites from Plants as Drugs or Leads against Protozoan Neglected Diseases-Part III: In-Silico Molecular Docking Investigations.Molecules (Basel, Switzerland) · 2016Review
- Twin Attributes of Tyrosyl-tRNA Synthetase of Leishmania donovani: A HOUSEKEEPING PROTEIN TRANSLATION ENZYME AND A MIMIC OF HOST CHEMOKINE.The Journal of biological chemistry · 2016Article
- A binding hotspot in Trypanosoma cruzi histidyl-tRNA synthetase revealed by fragment-based crystallographic cocktail screens.Acta crystallographica. Section D, Biological crystallography · 2015Article
- Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis.Chemical reviews · 2014Review
- Comparison of histidine recognition in human and trypanosomatid histidyl-tRNA synthetases.Biochimie · 2014Article
- Aminoacyl-tRNA synthetases as drug targets in eukaryotic parasites.International journal for parasitology. Drugs and drug resistance · 2014Review
- In-silico Leishmania target selectivity of antiparasitic terpenoids.Molecules (Basel, Switzerland) · 2013Article
- Crystal structures of Plasmodium falciparum cytosolic tryptophanyl-tRNA synthetase and its potential as a target for structure-guided drug design.Molecular and biochemical parasitology · 2013Article
- Unusual domain architecture of aminoacyl tRNA synthetases and their paralogs from Leishmania major.BMC genomics · 2012Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
The single tyrosyl-tRNA synthetase (TyrRS) gene in trypanosomatid genomes codes for a protein that is twice the length of TyrRS from virtually all other organisms. Each half of the double-length TyrRS contains a catalytic domain and an anticodon-binding domain; however, the two halves retain only 17% sequence identity to each other. The structural and functional consequences of this duplication and divergence are unclear. TyrRS normally forms a homodimer in which the active site of one monomer pairs with the anticodon-binding domain from the other. However, crystal structures of Leishmania major TyrRS show that, instead, the two halves of a single molecule form a pseudo-dimer resembling the canonical TyrRS dimer. Curiously, the C-terminal copy of the catalytic domain has lost the catalytically important HIGH and KMSKS motifs characteristic of class I aminoacyl-tRNA synthetases. Thus, the pseudo-dimer contains only one functional active site (contributed by the N-terminal half) and only one functional anticodon recognition site (contributed by the C-terminal half). Despite biochemical evidence for negative cooperativity between the two active sites of the usual TyrRS homodimer, previous structures have captured a crystallographically-imposed symmetric state. As the L. major TyrRS pseudo-dimer is inherently asymmetric, conformational variations observed near the active site may be relevant to understanding how the state of a single active site is communicated across the dimer interface. Furthermore, substantial differences between trypanosomal TyrRS and human homologs are promising for the design of inhibitors that selectively target the parasite enzyme.
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