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 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.

Background: Major fish allergens, including parvalbumin (PV), are heat stable and can withstand extensive cooking processes. Thus, the management of fish allergy generally relies on complete avoidance. Fish‐allergic patients may be advised to consume canned fish, as some fish‐allergic individuals have reported tolerance to canned fish. However, the safety of consuming canned fish has not been evaluated with comprehensive immunological and molecular analysis of canned fish products.Methods: We characterized the in vitro immunoreactivity of serum obtained from fish‐allergic subjects to canned fish. Seventeen canned fish products (salmon n = 8; tuna n = 7; sardine n = 2) were assessed for the content and integrity of PV using allergen‐specific antibodies. Subsequently, the sIgE binding of five selected products was evaluated for individual fish‐allergic patients (n = 53). Finally, sIgE‐binding proteins were identified by mass spectrometry.Results: The canned fish showed a markedly reduced PV content and binding to PV‐specific antibodies compared with conventionally cooked fish. However, PV and other heat‐stable fish allergens, including tropomyosin and collagen, still maintained their sIgE‐binding capacity. Of 53 patients, 66% showed sIgE binding to canned fish proteins. The canned sardine contained proteins bound to sIgE from 51% of patients, followed by canned salmon (43%–45%) and tuna (8%–17%). PV was the major allergen in canned salmon and sardine. Tropomyosin and/or collagen also showed sIgE binding.Conclusion: We showed that canned fish products may not be safe for all fish‐allergic patients. Canned fish products should only be considered into the diet of individuals with fish allergy, after detailed evaluation which may include in vitro diagnostics to various heat‐stable fish allergens and food challenge conducted in suitable environments.