Structure of <i>Plasmodium vivax</i> <i>N</i>-myristoyltransferase with inhibitor IMP-1088: exploring an NMT inhibitor for antimalarial therapy
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.
Authors
- Edward W. Tate (ORCID: https://orcid.org/0000-0003-2213-5814)
- Brad Hammerson
- Sandhya Subramanian (ORCID: https://orcid.org/0000-0002-5853-7498)
- Thomas E. Edwards (ORCID: https://orcid.org/0000-0002-0474-8003)
- Alexandra R. Reers (ORCID: https://orcid.org/0000-0003-2561-6648)
- Jan Abendroth (ORCID: https://orcid.org/0000-0002-8229-3243)
- Peter J. Myler (ORCID: https://orcid.org/0000-0002-0056-0513)
- Bart L. Staker (ORCID: https://orcid.org/0000-0001-9570-5086)
- Stanley Makumire (ORCID: https://orcid.org/0000-0003-4355-1382)
- Shane Taylor
- Donald D. Lorimer (ORCID: https://orcid.org/0000-0002-9638-8083)
- Oluwatoyin A. Asojo (ORCID: https://orcid.org/0000-0002-4043-2700)
- Stephen J. Mayclin (ORCID: https://orcid.org/0000-0002-1600-4554)
- Andrew Bell (ORCID: https://orcid.org/0000-0002-0581-9387)
- Graham Chakafana (ORCID: https://orcid.org/0000-0003-4539-3971)
- Cydni Bolling (ORCID: https://orcid.org/0009-0004-9996-5693)
- Alex Mendez
Institutions
- Center for Infectious Disease Research (US)
- Hampton University (US)
- Bridge Pharma (United States) (US)
- Dartmouth Cancer Center
- Imperial College London (GB)
- University of Oulu (FI)
Publication Details
- Journal
- Acta Crystallographica Section F Structural Biology Communications
- Published
- 2024-11-29
- DOI
- https://doi.org/10.1107/s2053230x24011348
- Citations
- 2
- Primary Topic
- Enzyme Structure and Function
- Type
- article
- Field-Weighted Citation Impact
- 0.23
Funders
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases