Structure of Plasmodium vivaxN-myristoyltransferase with inhibitor IMP-1088: exploring an NMT inhibitor for antimalarial therapy
Mendez, Alex; Bolling, Cydni; Taylor, Shane; Makumire, Stanley; Staker, Bart; Reers, Alexandra; Hammerson, Brad; Mayclin, Stephen J; Abendroth, Jan; Lorimer, Donald D; Edwards, Thomas E; Tate, Edward W; Subramanian, Sandhya; Bell, Andrew S; Myler, Peter J; Asojo, Oluwatoyin A; Chakafana, Graham (2025-01-01)
Wiley-Blackwell
01.01.2025
Mendez, A., Bolling, C., Taylor, S., Makumire, S., Staker, B., Reers, A., Hammerson, B., Mayclin, S. J., Abendroth, J., Lorimer, D. D., Edwards, T. E., Tate, E. W., Subramanian, S., Bell, A. S., Myler, P. J., Asojo, O. A., & Chakafana, G. (2025). Structure of Plasmodium vivax N -myristoyltransferase with inhibitor IMP-1088: Exploring an NMT inhibitor for antimalarial therapy. Acta Crystallographica Section F Structural Biology Communications, 81(1), 1–10. https://doi.org/10.1107/S2053230X24011348
https://creativecommons.org/licenses/by/4.0/
Published under a CC BY 4.0 licence.
https://creativecommons.org/licenses/by/4.0/
Published under a CC BY 4.0 licence.
https://creativecommons.org/licenses/by/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202501101117
https://urn.fi/URN:NBN:fi:oulu-202501101117
Tiivistelmä
Abstract
Plasmodium vivax, a significant contributor to global malaria cases, poses an escalating health burden on a substantial portion of the world's population. The increasing spread of P. vivax because of climate change underscores the development of new and rational drug-discovery approaches. The Seattle Structural Genomics Center for Infectious Diseases is taking a structure-based approach by investigating essential enzymes such as N-myristoyltransferase (NMT). P. vivax N-myristoyltransferase (PvNMT) is a promising target for the development of novel malaria treatments unlike current drugs, which target only the erythrocytic stages of the parasite. Here, the 1.8 Å resolution ternary structure of PvNMT in complex with myristoyl-CoA and IMP-1088, a validated NMT inhibitor, is reported. IMP-1088 is a validated nonpeptidic inhibitor and a ternary complex structure with human NMT has previously been reported. IMP-1088 binds similarly to PvNMT as to human NMT.
Plasmodium vivax, a significant contributor to global malaria cases, poses an escalating health burden on a substantial portion of the world's population. The increasing spread of P. vivax because of climate change underscores the development of new and rational drug-discovery approaches. The Seattle Structural Genomics Center for Infectious Diseases is taking a structure-based approach by investigating essential enzymes such as N-myristoyltransferase (NMT). P. vivax N-myristoyltransferase (PvNMT) is a promising target for the development of novel malaria treatments unlike current drugs, which target only the erythrocytic stages of the parasite. Here, the 1.8 Å resolution ternary structure of PvNMT in complex with myristoyl-CoA and IMP-1088, a validated NMT inhibitor, is reported. IMP-1088 is a validated nonpeptidic inhibitor and a ternary complex structure with human NMT has previously been reported. IMP-1088 binds similarly to PvNMT as to human NMT.
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