Related Experiment Video
Updated: Jul 7, 2026
07:37
Click-Chemistry Based Fluorometric Assay for Apolipoprotein N-acyltransferase from Enzyme Characterization to High-Throughput Screening
Published on: May 13, 2020
N-myristoyltransferase: a novel target
K K Prasad1, M P Toraskar, V J Kadam
1Department of Pharmaceutical Chemistry, Bharati Vidyapeeth's College of Pharmacy, Sector-8, C.B.D., Belapur, Navi Mumbai-400614, India.
Mini Reviews in Medicinal Chemistry
|February 22, 2008
Summary
Myristoyl-CoA:Protein N-myristoyltransferase (NMT) is a key enzyme targeted for drug development. Inhibitors like benzofurans show promise as antifungal agents by targeting fungal NMT.
Area of Science:
- Biochemistry
- Enzymology
- Medicinal Chemistry
Background:
- Myristoyl-CoA:Protein N-myristoyltransferase (NMT) is a cytosolic enzyme catalyzing the N-terminal myristoylation of proteins.
- This modification is crucial for the function of various eukaryotic and viral proteins.
- NMT represents a promising therapeutic target for anticancer, antiviral, and antifungal drug discovery.
Purpose of the Study:
- To investigate the potential of NMT as a drug target.
- To evaluate novel NMT inhibitors, specifically benzofuran and benzothiazole derivatives, for their therapeutic efficacy.
Main Methods:
- Enzyme kinetics and inhibition assays were employed to study NMT activity.
- In vivo studies were conducted to assess the antifungal activity of NMT inhibitors.
- Structure-activity relationship analysis of benzofuran and benzothiazole derivatives.
Main Results:
- Benzofuran and benzothiazole derivatives demonstrated significant in vivo antifungal activity.
- These compounds showed selectivity towards fungal NMT over human NMT.
- The study identified promising candidates for further drug development.
Conclusions:
- NMT is a validated target for antifungal drug development.
- Benzofuran and benzothiazole derivatives are effective inhibitors of fungal NMT.
- These findings support the advancement of NMT inhibitors as novel antifungal therapeutics.
Related Concept Videos
01:19Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
01:39Mitochondrial Precursor Proteins
Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70 chaperones are targetted to TOM20-TOM22 receptor complexes.
Most of the mitochondrial precursors...
Most of the mitochondrial precursors...
01:29Pharmacogenomics: Identification of New Drug Targets
Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
01:34Protein Transport into the Inner Mitochondrial Membrane
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
01:25Lipid Catabolism
Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...