Disease relevance of tetradecanoyl-CoA

• Human myristoyl-CoA synthetase and myristoyl-CoA:protein N-myristoyltransferase (hNmt) have been partially purified from an erythroleukemia cell line [1].
• Substrate specificity of Saccharomyces cerevisiae myristoyl-CoA: protein N-myristoyltransferase. Analysis of fatty acid analogs containing carbonyl groups, nitrogen heteroatoms, and nitrogen heterocycles in an in vitro enzyme assay and subsequent identification of inhibitors of human immunodeficiency virus I replication [2].
• An unusual Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein (ACP) synthase III (mtFabH) has been identified, purified, and shown to catalyze a Claisen-type condensation between long chain acyl-CoA substrates such as myristoyl-CoA (C(14)) and malonyl-ACP [3].
• Characterization of a polyhistidine-tagged form of human myristoyl-CoA: protein N-myristoyltransferase produced in Escherichia coli [4].
• Cyanide-insensitive beta-oxidation in control livers showed optimal specificity for lauroyl- and myristoyl-CoA and this pattern remained unchanged by sepsis [5].

High impact information on tetradecanoyl-CoA

• Together, the data indicate that nmt-181 represents a sensitive reporter of the myristoyl-CoA pools utilized by NMT [6].
• Targeted gene replacement demonstrates that myristoyl-CoA: protein N-myristoyltransferase is essential for viability of Cryptococcus neoformans [7].
• To determine which lysine(s) are acylated, a series of synthetic peptides containing all lysines found in the IL-1 alpha N-terminal propiece were used in an in vitro myristoylation assay containing peptide, myristoyl-CoA, and monocyte lysate as enzyme source [8].
• Herein, we demonstrate the highly selective iPLA2beta-catalyzed hydrolysis of saturated long-chain fatty acyl-CoAs (palmitoyl-CoA approximately myristoyl-CoA >> stearoyl-CoA >> oleoyl-CoA approximately = arachidonoyl-CoA) present either as monomers in solution or guests in host membrane bilayers [9].
• We speculate that the trypanosome acyl-CoA-binding protein plays an active role in supplying myristoyl-CoA to the fatty acid remodeling machinery in the parasite [10].

Biological context of tetradecanoyl-CoA

• Comparison of the in vitro kinetic properties of a number of synthetic octapeptide substrates of NMT using myristoyl-CoA or 11-oxymyristoyl-CoA indicated that there is an interaction between the acyl-CoA and peptide binding sites of this acyltransferase [11].
• An alternate method for in vitro acylation of polypeptides in the luminescent system was developed using tetradecanoyl-CoA [12].
• In aqueous buffers at pH 7, the 32-kDa protein catalyzes the hydrolysis of tetradecanoyl-CoA at a low rate (0.01 mumol/min/mg) to form free fatty acids [13].
• Fatty acyl chain length was important, C-13 to C-16 fatty acyl-CoA esters all fully blocking the action of GTP; the IC50 for myristoyl-CoA was also 0.5 microM [14].
• The substrate specificity of Saccharomyces cerevisiae myristoyl-CoA: protein N-myristoyltransferase. Polar probes of the enzyme's myristoyl-CoA recognition site [15].

Anatomical context of tetradecanoyl-CoA

• N-myristoyl transferase (NMT) catalyzes the transfer of the fatty acid myristate from myristoyl-CoA to the N-terminal glycine of substrate proteins, and is found only in eukaryotic cells [16].
• Only the combination of the Nmt mutant (nmt451Dp; reduced affinity for myristoyl-CoA) and loss of Faa4p produced a dramatic loss of colony-forming units (CFU) [17].
• Cardiac muscle NMT has a higher affinity for myristoyl-CoA than toward palmitoyl-CoA [18].
• Immunocytochemical characterization and subcellular localization of human myristoyl-CoA: protein N-myristoyltransferase in HeLa cells [19].
• Reconstitution with liposomes of a range of compositions restored the K0.5 for myristoyl-CoA to values similar to that seen in native membranes [20].

Associations of tetradecanoyl-CoA with other chemical compounds

• Product inhibition studies indicate that Nmt1p has an ordered Bi Bi reaction mechanism with myristoyl-CoA binding to the apo-enzyme to form a high affinity binary complex followed by binding of peptide with subsequent release of CoA and then the myristoylpeptide product [21].
• The nonhydrolyzable myristoyl-CoA analog, S-(2-oxopentadecyl)-CoA, blocked the GTP effect identically to myristoyl- and palmitoyl-CoA (IC50 = 0.5 microM); thus, fatty acyl transfer is not required, indicating that blockade is due to a direct allosteric modification of a component of the GTP-activated process by acyl-CoA esters [14].
• Nmt1p transfers myristate (C14:0), from myristoyl-CoA to the amino-terminal Gly residue of several essential cellular proteins [22].
• The acyl-CoA reductase had a high specificity for NADPH with a Km value of 5 microM at optimal concentrations of tetradecanoyl-CoA (5-10 microM) [23].
• Incubation of purified NMT with [1-14C] myristoyl-CoA, followed by chymotryptic digestion, denaturing polyacrylamide gel electrophoresis, and treatment with hydroxylamine yielded results that are highly suggestive of a covalent ester-linked acyl-enzyme complex [24].

Gene context of tetradecanoyl-CoA

• The photopeptides can be specifically crosslinked to chymotryptic fragments of Nmt1p in the presence but not in the absence of a nonhydrolyzable myristoyl-CoA analog, S-(2-oxo)pentadecyl-CoA [25].
• N-myristoylation of Arf proteins in Candida albicans: an in vivo assay for evaluating antifungal inhibitors of myristoyl-CoA: protein N-myristoyltransferase [26].
• The action of myristic acid was abrogated by inhibition of FACL3 activity, suggesting that the enhancement in the downregulation of FAS expression by vitamin D3 is due to the formation of myristoyl-CoA [27].
• This product can be remyristoylated in the presence of myristoyl-CoA and N-myristoyl transferase, demonstrating that cycles of myristoylation/demyristoylation of MARCKS can be achieved in vitro [28].
• Sequence and expression of Drosophila myristoyl-CoA: protein N-myristoyl transferase: evidence for proteolytic processing and membrane localisation [29].

Analytical, diagnostic and therapeutic context of tetradecanoyl-CoA

• High performance liquid chromatography analysis of the intracellular acyl-CoA esters revealed an abnormal accumulation of myristoyl-CoA (C14-CoA) in cells cultivated close to the nonpermissive temperature [30].
• Size-exclusion chromatography of this material in the presence of myristoyl-CoA yielded two peaks of enzyme activity with apparent molecular masses of 66 kDa and 43 kDa [31].
• The authors have tested the ability of unlabelled acyl-CoAs to compete with [(3)H] myristoyl-CoA transfer, the efficacy of an NMT inhibitory protein (NIP(71)), and acyl-CoA affinity chromatography was used to isolate endogenous NMT inhibitory factor(s) from bovine heart and retina tissue homogenates [32].
• The molecular structure of the ternary complex of Saccharomyces cerevisiae Nmt1p with a bound non-hydrolyzable myristoyl-CoA analog, S-(2-oxopentadecyl)-CoA, and a competitive peptidomimetic inhibitor, SC-58272, was solved to 2.9 A resolution by X-ray crystallography [33].
• Thermodynamic studies of myristoyl-CoA: protein N-myristoyltransferase using isothermal titration calorimetry [34].

References