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N-myristoyltransferases: structure, function, disease, and inhibitors
Suyang Yao1, Xiaofang Wang2, Shuyu Liu1
1Key Laboratory of Pharmaceutical Quality Control of Hebei Province, College of Pharmaceutical Sciences, Hebei University, Baoding, Hebei 071002, China.
Abstract:
N-myristoyltransferases (NMTs) catalyze protein N-myristoylation, which regulates protein localization and function. Notably, NMT1 is overexpressed in multiple cancers and promotes cancer survival primarily through N-myristoylation of its substrate proteins. NMT2-deficient cancer cells become more dependent on NMT1, further emphasizing its crucial role in this disease. In this review, we outline the structure, catalytic and inhibitory mechanisms, and pathological functions of NMTs, and provide an overview of inhibitors targeting distinct active sites. We also discuss future research directions and challenges, including the development of selective NMT inhibitors (NMTi), NMTi-antibody-drug conjugate (ADC) optimization, and biomarker exploration.
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