Structural basis of malaria parasite phenylalanine tRNA-synthetase inhibition by bicyclic azetidines

Manmohan Sharma; Nipun Malhotra; Manickam Yogavel; Karl Harlos; Bruno Melillo; Eamon Comer; Arthur Gonse; Suhel Parvez; Branko Mitasev; Francis G. Fang; Stuart L. Schreiber; Amit Sharma

doi:10.1038/s41467-020-20478-5

Nature Communications (Jan 2021)

Structural basis of malaria parasite phenylalanine tRNA-synthetase inhibition by bicyclic azetidines

Manmohan Sharma,
Nipun Malhotra,
Manickam Yogavel,
Karl Harlos,
Bruno Melillo,
Eamon Comer,
Arthur Gonse,
Suhel Parvez,
Branko Mitasev,
Francis G. Fang,
Stuart L. Schreiber,
Amit Sharma

Affiliations

Manmohan Sharma: Molecular Medicine, Structural Parasitology Group, International Centre for Genetic Engineering and Biotechnology
Nipun Malhotra: Molecular Medicine, Structural Parasitology Group, International Centre for Genetic Engineering and Biotechnology
Manickam Yogavel: Molecular Medicine, Structural Parasitology Group, International Centre for Genetic Engineering and Biotechnology
Karl Harlos: Division of Structural Biology, Welcome Centre for Human Genetics, University of Oxford
Bruno Melillo: Chemical Biology and Therapeutics Science Program, Broad Institute of Harvard and MIT
Eamon Comer: Chemical Biology and Therapeutics Science Program, Broad Institute of Harvard and MIT
Arthur Gonse: Chemical Biology and Therapeutics Science Program, Broad Institute of Harvard and MIT
Suhel Parvez: Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard
Branko Mitasev: Eisai Inc.
Francis G. Fang: Eisai Inc.
Stuart L. Schreiber: Chemical Biology and Therapeutics Science Program, Broad Institute of Harvard and MIT
Amit Sharma: Molecular Medicine, Structural Parasitology Group, International Centre for Genetic Engineering and Biotechnology

DOI: https://doi.org/10.1038/s41467-020-20478-5
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 10

Abstract

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Bicyclic azetidine inhibitors are promising antimalarials that target the Plasmodium cytosolic phenylalanine tRNAsynthetase (cFRS). Here, Sharma et al. provide the biochemical and structural basis of its mechanism using co-crystal structure of PvcFRS with BRD1389.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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