Disease relevance of NMT1

• The protein coding sequence was expressed in Escherichia coli resulting in the production of functionally active 50-kDa NMT [1].
• Previously, we reported that NMT activity is higher in colonic epithelial neoplasms than in normal-appearing colonic tissue and that the increase in NMT activity appears at an early stage in colonic carcinogenesis [2].

High impact information on NMT1

• The finding that retinal recoverin is myristoylated at its amino terminus led us to coexpress the recombinant protein and N-myristoyltransferase (EC 2.3.1.97) [3].
• N-Myristoyltransferase (NMT) catalyzes the co-translational addition of myristic acid to the N-terminal glycine of many cellular, viral, and fungal proteins which are essential to normal cell functioning and/or are potential therapeutic targets [4].
• The prominent 60 kDa and minor 57-, 53-, 49-, and 47-kDa NMT immunoblotted subunits co-migrate with five of nine silver-stained proteins in an enzyme preparation purified > 7,000-fold with approximately 50% yield by selective elution from octyl-agarose with the myristoyl-CoA analog, S-(2-ketopentadecyl)-CoA [4].
• Myristoyl-CoA:protein N-myristoyltransferase (NMT) catalyzes the addition of myristate to the amino-terminal glycine residue of a number of eukaryotic proteins [5].
• Myristoyl-coA:protein N-myristoyltransferase from bovine cardiac muscle: molecular cloning, kinetic analysis, and in vitro proteolytic cleavage by m-calpain [6].

Biological context of NMT1

• We also present evidence that there are two copies of Type II NMT in the bovine genome [7].
• Cardiac tissue expresses high levels of cAMP-dependent protein kinase whose catalytic subunit is myristoylated; however, cardiac muscle extracts were found to contain low NMT activities [6].
• None of the compounds showed significant substrate activity for NMT, a fact that is consistent with our proposed active site binding model [8].
• An NMT protein inhibitor (NIP71) isolated from the particulate fraction of bovine brain (King MJ and Sharma RK: Biochem J 291:635-639, 1993) potently inhibited highly purified NMT activity (IC50 23.7 nM) [9].
• Myristoyl CoA:protein N-myristoyltransferase (NMT) catalyses the attachment of myristate to the amino-terminal glycine residue of various signal transduction proteins [10].

Anatomical context of NMT1

• Activity measurements demonstrated that brain contained the highest NMT activity followed by spleen, lung, kidney, heart, skeletal muscle, pancreas, and liver [1].
• The expression of mRNA and protein levels in cardiac muscle is not correlated with NMT activities, suggesting the presence of regulators of the enzyme activity [6].
• Ultrastructural and immunolocalization of NMT utilizing the immunogold labeling technique demonstrated cytoplasmic distribution with occasional mitochondrial and myofilaments localization of the NMT antibody [6].
• They inhibited NMT from human, rat, and bovine adrenal glands but were slightly less effective against those enzymes than against the rabbit adrenal enzyme [11].
• The inhibitory activity of crude homogenate on recombinant human NMT activity was found to be greater for optic nerve and choroid [12].

Associations of NMT1 with chemical compounds

• The enzyme myristoyl-CoA:protein N-myristoyltransferase (NMT; EC 2.3.1.97) catalyses the transfer of myristic acid to the N-terminal glycine residue of cell and viral proteins [13].
• PURPOSE: The mammalian myristoyl-CoA:protein N-myristoyltransferase (NMT) family consists of Type I and Type II enzymes that typically catalyze the addition of myristic acid (14:0) to the N-terminus of specific proteins using myristoyl-Coenzyme A as a donor [7].
• Therefore, the focus of this work has been to identify NMT isoforms that may be unique or differentially expressed in bovine retina that may utilize acyl-CoAs in addition to myristoyl-CoA [7].
• Myristoyl-CoA:protein N-myristoyltransferase (NMT) is an essential eukaryotic enzyme that catalyzes the cotranslational transfer of myristate to the NH2-terminal glycine residue of a number of important proteins of diverse function [1].
• MyristoylCoA:protein N-myristoyltransferase (Nmt, EC 2.3.1.97), a member of the GCN5 acetyltransferase (GNAT) superfamily, is an essential eukaryotic enzyme that catalyzes covalent attachment of myristate (C14:0) to the N-terminal Gly of proteins involved in myriad cellular functions [14].

Analytical, diagnostic and therapeutic context of NMT1

• Western blot analysis of various bovine tissues with human NMT peptide antibody indicated a common prominent immunoreactive band with an apparent molecular mass of 48.5-50 kDa in all tissues [1].
• Molecular cloning and biochemical characterization of bovine spleen myristoyl CoA:protein N-myristoyltransferase [1].
• Southern blotting was done to determine if one or more genomic copies of Type II NMT are present in the bovine genome [7].
• Gel filtration chromatography of partially purified NMT at low to moderate ionic strength yields NMT activity eluting as 391 +/- 52 and 126 +/- 17 kDa peaks as well as activity which profiles the protein fractions and likely results from NMT nonspecifically associating with background proteins and/or column matrix [4].
• Northern blot analysis of bovine heart poly(A)+ RNA probed with bovine spleen NMT cDNA revealed a 1.7-kb mRNA [6].

References