Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy-Reference-Cited by-同舟云学术

Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy

Published:2022-06-03 Issue:6597 Volume:376 Page:1074-1079
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Xie Stanley C.¹^ORCID,Metcalfe Riley D.¹^ORCID,Dunn Elyse¹^ORCID,Morton Craig J.¹^ORCID,Huang Shih-Chung²^ORCID,Puhalovich Tanya¹^ORCID,Du Yawei¹^ORCID,Wittlin Sergio³⁴,Nie Shuai⁵^ORCID,Luth Madeline R.⁶^ORCID,Ma Liting²,Kim Mi-Sook²,Pasaje Charisse Flerida A.⁷^ORCID,Kumpornsin Krittikorn⁸^ORCID,Giannangelo Carlo⁹^ORCID,Houghton Fiona J.¹^ORCID,Churchyard Alisje¹⁰^ORCID,Famodimu Mufuliat T.¹⁰^ORCID,Barry Daniel C.¹^ORCID,Gillett David L.¹^ORCID,Dey Sumanta⁷^ORCID,Kosasih Clara C.¹^ORCID,Newman William¹^ORCID,Niles Jacquin C.⁷^ORCID,Lee Marcus C. S.⁸^ORCID,Baum Jake¹⁰^ORCID,Ottilie Sabine⁶,Winzeler Elizabeth A.⁶^ORCID,Creek Darren J.⁹^ORCID,Williamson Nicholas⁵^ORCID,Parker Michael W.¹¹¹^ORCID,Brand Stephen¹²^ORCID,Langston Steven P.²^ORCID,Dick Lawrence R.¹¹³^ORCID,Griffin Michael D.W.¹^ORCID,Gould Alexandra E.²^ORCID,Tilley Leann¹^ORCID

Affiliation:

1. Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.

2. Takeda Development Center Americas, Inc., Cambridge, MA 02139, USA.

3. Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland.

4. University of Basel, 4003 Basel, Switzerland.

5. Melbourne Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Melbourne, VIC 3010, Australia.

6. Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.

7. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

8. Parasites and Microbes Programme, Wellcome Sanger Institute, Hinxton CB10 1SA, UK.

9. Drug Delivery, Disposition, and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.

10. Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.

11. St. Vincent’s Institute of Medical Research, Fitzroy, VIC 3065, Australia.

12. Medicines for Malaria Venture, P.O. Box 1826, 20, Route de Pré-Bois, 1215 Geneva 15, Switzerland.

13. Seofon Consulting, Natick, MA 01760, USA.

Abstract

Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) are attractive drug targets, and we present class I and II aaRSs as previously unrecognized targets for adenosine 5′-monophosphate–mimicking nucleoside sulfamates. The target enzyme catalyzes the formation of an inhibitory amino acid–sulfamate conjugate through a reaction-hijacking mechanism. We identified adenosine 5′-sulfamate as a broad-specificity compound that hijacks a range of aaRSs and ML901 as a specific reagent a specific reagent that hijacks a single aaRS in the malaria parasite Plasmodium falciparum , namely tyrosine RS ( Pf YRS). ML901 exerts whole-life-cycle–killing activity with low nanomolar potency and single-dose efficacy in a mouse model of malaria. X-ray crystallographic studies of plasmodium and human YRSs reveal differential flexibility of a loop over the catalytic site that underpins differential susceptibility to reaction hijacking by ML901.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference72 articles.

1. WHO “World Malaria Report 2021” (2021); https://www.who.int/publications/i/item/9789240040496.

2. Determinants of dihydroartemisinin-piperaquine treatment failure in Plasmodium falciparum malaria in Cambodia, Thailand, and Vietnam: a prospective clinical, pharmacological, and genetic study

3. Evidence of Artemisinin-Resistant Malaria in Africa

4. Substrate-Assisted Inhibition of Ubiquitin-like Protein-Activating Enzymes: The NEDD8 E1 Inhibitor MLN4924 Forms a NEDD8-AMP Mimetic In Situ

5. J. Florini in Antibiotics I: Mechanism of Action G. Shaw Ed. (Springer 1967) pp. 427–433.

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