Inhibitors of Methionyl-tRNA Synthetase Have Potent Activity against Giardia intestinalis Trophozoites
نویسندگان
چکیده
منابع مشابه
Inhibitors of methionyl-tRNA synthetase have potent activity against Giardia intestinalis trophozoites.
The methionyl-tRNA synthetase (MetRS) is a novel drug target for the protozoan pathogen Giardia intestinalis. This protist contains a single MetRS that is distinct from the human cytoplasmic MetRS. A panel of MetRS inhibitors was tested against recombinant Giardia MetRS, Giardia trophozoites, and mammalian cell lines. The best compounds inhibited trophozoite growth at 500 nM (metronidazole did ...
متن کاملMethionyl-tRNA synthetase.
Methionyl-tRNA synthetase (MetRS) belongs to the family of 20 enzymes essential for protein biosynthesis. It links covalently methionine with its cognate tRNA. Crystal structures solved for bacterial MetRSs have given a number of interesting insights into enzyme architecture and methionylation catalysis. A comparison of sequences of MetRSs belonging to all kingdoms of life, as well as numerous ...
متن کاملVariable sensitivity to bacterial methionyl-tRNA synthetase inhibitors reveals subpopulations of Streptococcus pneumoniae with two distinct methionyl-tRNA synthetase genes.
As reported previously (J. R. Jarvest et al., J. Med. Chem. 45:1952-1962, 2002), potent inhibitors (at nanomolar concentrations) of Staphylococcus aureus methionyl-tRNA synthetase (MetS; encoded by metS1) have been derived from a high-throughput screening assay hit. Optimized compounds showed excellent activities against staphylococcal and enterococcal pathogens. We report on the bimodal suscep...
متن کاملPharmacophore identification and virtual screening for methionyl-tRNA synthetase inhibitors.
Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes involved in protein biosynthesis in all living organisms and are an unexploited antibacterial targets, as many strains of bacteria have become resistant to all established classes of antibiotics. Therefore, the main aim of this study is to discover new lead molecules which would be useful as anti-bacterial compounds. Pharmacophore models ...
متن کاملPromiscuous Methionyl-tRNA Synthetase Mediates Adaptive Mistranslation against Oxidative Stresses
Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. Research Institute of Pharmaceutical Sciences, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 151-742, Korea. Department of Molecular Bioscience, Kang Won National University, Chuncheon-si, Gangwon-do, 200-701, Korea. School of Life Science and Biotechno...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
ژورنال
عنوان ژورنال: Antimicrobial Agents and Chemotherapy
سال: 2015
ISSN: 0066-4804,1098-6596
DOI: 10.1128/aac.01573-15