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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.
N-myristoyltransferases (NMTs) are key enzymes in cancer. This review details NMT structure, function, and inhibitors, highlighting NMT1
Area of Science:
- Biochemistry and Molecular Biology
- Cancer Research
- Drug Discovery
Background:
- N-myristoyltransferases (NMTs) catalyze protein N-myristoylation, a critical post-translational modification regulating protein function and localization.
- NMT1 is frequently overexpressed in various cancers, significantly contributing to cancer cell survival.
- Cancer cells lacking NMT2 exhibit increased reliance on NMT1, underscoring its vital role in oncogenesis.
Purpose of the Study:
- To provide a comprehensive review of N-myristoyltransferases (NMTs), focusing on their structure, catalytic mechanisms, and pathological roles in cancer.
- To summarize current NMT inhibitors targeting distinct active sites and discuss their therapeutic potential.
- To explore future research avenues, including selective NMT inhibitor development, antibody-drug conjugate optimization, and biomarker identification.
Main Methods:
- Literature review of NMT structure, function, and inhibition.
- Analysis of pathological roles of NMT1 in cancer survival.
- Overview of existing and emerging NMT inhibitors.
Main Results:
- NMTs play a crucial role in protein myristoylation, impacting protein localization and function.
- NMT1 overexpression is a hallmark of many cancers, promoting tumor cell survival.
- NMT inhibitors show promise for cancer therapy, with ongoing efforts in developing selective agents and antibody-drug conjugates.
Conclusions:
- NMTs, particularly NMT1, represent significant therapeutic targets in oncology.
- Further research into selective NMT inhibitors and combination therapies is warranted.
- Development of biomarkers for NMT activity could enhance targeted cancer treatment strategies.
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