Disease relevance of Nmt1

• The F52 protein also was myristoylated in E. coli by co-expression with N-myristoyltransferase [1].

High impact information on Nmt1

• These heteroatom-containing analogs serve as alternative substrates for mammalian myristoyl-CoA:protein N-myristoyltransferase (EC 2.3.1.97) and offer the opportunity to explore structure/function relationships of myristate in N-myristoyl proteins [2].
• The Nmt2 mRNA could be detected in Nmt1-/- ES cells, but the total NMT activity levels were reduced by approximately 95%, suggesting that Nmt2 contributes little to total enzyme activity levels in these early embryo cells [3].
• We conclude that Nmt1 is not essential for the viability of mammalian cells but is required for development, likely because it is the principal N-myristoyltransferase in early embryogenesis [3].
• Intercrosses of Nmt1+/- mice yielded no viable homozygotes (Nmt1-/-), and heterozygotes were born at a less than predicted frequency [3].
• N-Myristoyltransferase (NMT) transfers myristate to an amino-terminal glycine of many eukaryotic proteins [3].

Biological context of Nmt1

• Metabolic activation of 2-substituted derivatives of myristic acid to form potent inhibitors of myristoyl CoA:protein N-myristoyltransferase [4].
• Tissue distribution, flow cytometry and competition analysis indicated differences between identified T lymphocyte markers, including Thy-1, and the autoantigen identified by NMT-1 maAbs in this study [5].

Anatomical context of Nmt1

• The enzyme responsible for this modification, myristoyl CoA:protein N-myristoyltransferase (NMT), can be measured in cell-free systems by following the transfer of [3H]myristate from [3H]myristoyl CoA to a synthetic peptide substrate [6].
• In this study, NMT-1 mAbs have been shown to identify a thymocyte cell surface molecule (Immature Thymocyte Marker-1, ITM-1) expressed on 86.2 to 90.8% of CD4+CD8+CD3-/lo/int cells within the thymus of Balb/c, CBA, C57B1/6, 129 Rej, A/J and AKR mice [7].
• Furthermore, multiparameter flow cytometry demonstrated an association between the expression of the cell surface autoantigen identified by NMT-1 maAbs and thymocyte maturation as 94-97% of the CD4+ CD8+ thymocytes expressed the identified autoantigen which was largely absent from CD3+ thymocytes and not expressed in the peripheral immune system [5].
• Thymus-restricted expression of the identified autoantigen was demonstrated by the lack of detectable reactivity of NMT-1 maAbs to cell surface molecules of Balb/c mouse splenocytes, PBLs, lymph node, peritoneal and bone marrow cells and tissues including brain, liver and kidney [5].
• In the present study, the specificity of monoclonal IgM kappa anti-thymocyte autoantibodies from hybridoma NMT-1 (NMT-1 maAbs), derived from the spleen of an unimmunized 8-day-old inbred Balb/c mouse has been examined [5].

Associations of Nmt1 with chemical compounds

• Compared to other species that possess a single functional myristoyl-CoA: protein N-myristoyltransferase gene copy, human, mouse and cow possess 2 NMT genes, and more than 2 protein isoforms [8].
• Myristoylation is catalyzed by an enzyme activity, N-myristoyltransferase (NMT), which transfers myristic acid from myristoyl coenzyme A to the amino group of a protein's N-terminal glycine residue [9].
• The results showed that in scr -/- mice the effect of TCDD was less in the case of mRNA expression of PDGF(AA), STAT3, C/EPBbeta, NMT-1, and AP-2gamma in addition to c-src as compared to scr +/+ mice [10].

Other interactions of Nmt1

• 5. Northern blots revealed lower levels of Nmt2 expression in early development than at later time points, a potential explanation for the demise of Nmt1-/- embryos [3].

Analytical, diagnostic and therapeutic context of Nmt1

• Comparison of these immunoprecipitation profiles with those produced by rat IgG2b anti-Thy-1 antibodies indicated that NMT-1 mAbs recognized a subspecies of the Thy-1 molecule [7].

References