Using 5'-rapid amplification of cDNA ends, we have identified an extended 5'-end of mRNA coding for human myristoyl-CoA:protein N-myristoyltransferase (NMT). PCR using primers based on this new 5'-sequence and reverse primers within the currently accepted coding sequence of the enzyme resulted in the identification of a novel splice variant of NMT. In vitro translation of these cDNAs resulted in the production of proteins with apparent molecular masses of 63 kDa and 48 kDa. Immunoprecipitation of NMT from human cell lines and immunoblotting of a range of rat tissues has identified proteins with molecular masses corresponding to those derived from these cDNAs, and provided evidence that their relative abundance differs among tissues. Our results provide evidence that this enzyme exists in different forms resulting from alternative splicing of the mRNA.
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http://dx.doi.org/10.1042/bj3330491 | DOI Listing |
Exp Parasitol
January 2025
Natural Products Chemistry Laboratory, State University of Ceará, Fortaleza, Brazil. Electronic address:
The current treatment of leishmaniasis is confronted with significant challenges, including limited efficacy, adverse effects, and parasite resistance to drugs. The search for alternative therapeutic options, including the utilization of natural products, has demonstrated considerable promise. In this study, the antileishmanial activity of the flavonoid hesperetin against Leishmania donovani, the causative agent of visceral leishmaniasis, was reported for the first time.
View Article and Find Full Text PDFBioorg Med Chem Lett
January 2025
Department of Biochemistry, University of Washington, Seattle, WA 98195, United States. Electronic address:
Cryptosporidium parvum is a protozoan parasite that causes severe diarrheal illness in children and each year nearly 50,000 children under age 5 die due to the disease. Despite tremendous research efforts, there remains a lack of effective therapies and vaccines. Novel inhibitors against N-myristoyltransferase of C.
View Article and Find Full Text PDFFront Chem
November 2024
NanoStruc Research Group, Chemistry Department, Faculty of Science, Helwan University, Cairo, Egypt.
Background: has long been recognized for its therapeutic properties against various diseases. Among these is leishmaniasis, a parasitic infection that remains a global health challenge. Targeting Leishmania N-myristoyltransferase (NMT), a crucial enzyme for parasite survival, represents a promising therapeutic approach.
View Article and Find Full Text PDFActa Crystallogr F Struct Biol Commun
January 2025
Chemistry and Biochemistry Department, Hampton University, 200 William R. Harvey Way, Hampton, VA 23668, USA.
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.
View Article and Find Full Text PDFPLoS Pathog
December 2024
Unité de Biologie des Infections Virales Emergentes, Institut Pasteur, Université Paris Cité, Lyon, France.
Several Old World and New World Mammarenavirus are responsible for hemorrhagic fever in humans. These enveloped viruses have a bi-segmented ambisense RNA genome that encodes four proteins. All Mammarenavirus identified to date share a common dependency on myristoylation: the addition of the C14 myristic acid on the N-terminal G2 residue on two of their proteins.
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