Acylation, of proteins

Staudinger ligation techniques also can be used to detect post-translational modification of proteins in vivo. Hang et al. (2007) developed a method to monitor fatty acid acylation of proteins using azido-fatty acids fed to cells. The two major types of fatty acid acylation,... 

H. Cai, F. P. Guengerich, Acylation of Protein Lysines by Trichloroethylene Oxide , Chem. Res. Toxicol. 2000,13, 327 - 335 H. Cai, F. P. Guengerich, Reaction of Trichloroethylene and Trichloroethylene Oxide with Cytochrome P450 Enzymes Inactivation and Sites of Modification , Chem. Res. Toxicol. 2001, 14, 451 - 458. 

Acylation of protein amino groups by the mixed anhydride of para-AtC6H4COOH can be achieved by the following reaction sequence [Eqs. (15)-(17)]. 

As discussed for N-myristoylation and S-prenylation, even S-acylation of proteins with a fatty acid which in the vast majority of cases is the C16 0 palmitic acid, plays a fundamental role in the cellular signal-transduction process (Table l). 2-5 14 While N-myristoylation and S-prenylation are permanent protein modifications due to the amide- and sulfide-type linkage, the thioester bond between palmitic acid and the peptide chain is rather labile and palmi-toylation is referred to as a dynamic modification. 64 This reversibility plays a crucial role in the modulation of protein functions since the presence or absence of a palmitoyl chain can determine the membrane localization of the protein and can also be used to regulate the interactions of these proteins with other proteins. Furthermore, a unique consensus sequence for protein palmitoylation has not been found, in contrast to the strict consensus sequences required for N-myristoylation and S-prenylation. Palmitoylation can occur at N- or C-terminal parts of the polypeptide chain depending on the protein family and often coexists with other types of lipidation (see Section 6.4.1.4). Given the diversity of protein sequences... 

Acylated Protein Hydrolysates. These surfactants are prepared by acylation of protein hydrolysates with fatty acids or acid chlorides. The hydrolysates are variable in composition, depending on the degree of hydrolysis. Collagen from leather (qv) processing is a common protein source. Acylated protein hydrolysates (Maypon, by Inotex Chemical Company) are mild surfactants recommended for personal-care products (see Cosmetics). 

Acylated Protein Hydrolysates. These surfactants are prepared by acylation of protein hydrolysates with fatty acids or acid chlorides. 

Resh MD. Fatty acylation of proteins new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochim Biophys Acta 1999 1451(1) 1-16. 

Schmidt, M. F. 1982. Acylation of proteins—a new type of modification of membrane glycoproteins. Trends Biochem. Sci. 7 322-324. 

Pantothenic acid has a central role in energy-yielding metabolism as the functional moiety of coenzyme A (CoA), in the biosynthesis of fatty acids as the prosthetic group of acyl carrier protein, and through its role in CoA in the mitochondrial elongation of fatty acids the biosynthesis of steroids, porphyrins, and acetylcholine and other acyl transfer reactions, including postsynthetic acylation of proteins. Perhaps 4% of all known enzymes utilize CoA derivatives. CoA is also bound by disulfide links to protein cysteine residues in sporulating bacteria, where it may be involved with heat resistance of the spores, and in mitochondrial proteins, where it seems to be involved in the assembly of active cytochrome c oxidase and ATP synthetase complexes. 

Fatty acylation of proteins is a common posttranslational modification that blocks sequencing of the N-terminal amino acids by Edman techniques. Mass spectrometry can play an essential role in such sequencing, but it is not always trivial to locate the blocked N-terminal peptide. Besides acetylation, acylation of amino acids with longer-chain fatty acids (e.g., myristic acid) has been reported. 

There are really two factors to be considered. First, the capability of a particular drug to cause the event which I just described, and secondly the capability of a drug administered to a person in which this process has taken place to be immediately recognized as antigenic and to elicit an anaphylactic reaction. A number of different chemical reactions have been associated with this phenomenon. One of them is simple acylation of protein by the / -lactam. Inasmuch as the mechanism of action of both the penicillins and cephalosporins is also thought to involve acylation by the -lactam, I think that it is very unlikely that there will ever be a -lactam antibiotic which is active and which will not in some patients form antigenic material by this same mechanism. It is my impression that cephalosporins have a lesser tendency to sensitize than some penicillins and that not all penicillin-sensitive people react to a given cephalosporin. The differences are probably quantitative and will never be qualitative. 

A family of protein acyltransferases (PATs) is responsible for S-acylation of proteins in cells (S. Lobo, 2002 A. Roth, 2002) [8]. Members of this family are characterized by the presence of a cysteine-rich domain containing a DHHC (Asp-His-His-Cys) motif. PATs are polytopic membrane proteins with the putative catalytic DHHC motif localized to a cytoplasmic loop between transmembrane spans. Some PATs function alone whereas others, such as the yeast Ras PAT Erf2, require a cytoplasmic protein, Erf4, for activity. It is likely that particular classes of substrate have a dedicated PAT that accounts for most, if not all, of their S-acylation. For example, Swflp modifies SNARE proteins and other monotopic membrane proteins with a juxtamembrane cysteine residue. The yeast vacuolar protein Vac8 is mainly S-acylated by the vacuolar DHHC protein Pfa3 (J.E. Smotrys,... 

The acyl-generation reaction, Eq. (8), has been visualized as a reductive acylation of protein-bound lipoic acid. As will be seen below, this reaction is now belitwod to consist of two steps an oxidation of the 2-hydroxyalkyl-thiamine pyrophcjsphatc to 2-aoylthiaminc pyrophosphate with a concomitant reduction of bound lipoic acid, and a transfer of (he acyl group of 2-acylthiamine pyrophosphate to the bound dihydrolipoic acid (Das el al., 19(il). An enzymatic component which contains bound lipoic acid and apparently catalyzes reactions (8) and (9) has been isolated from the E. mli pyruvate dehydrogenation complex (Koike and Reed, 1961). This component, designated lipoyl-Ea in Fig. 1, has been tentatively named lipoic reductase-transacetylase. 

Schlesinger MJ, Magee Al, Schmidt MFG (1980) Fatty acid acylation of proteins in cultured cells. J Biol Chem 255 10021-10024... 

As described earlier, fatty acylation gives rise to the dramatic changes in the surface properties of proteins. If the attachment of fatty acyl groups to proteins is carried out not via chemical reaction but via enzyme-catalyzed reaction, the range of application of fatty acylated proteins should be expanded, especially in the food industry. However, most attempts concerning the fatty acylation of proteins via enzymatic methods have not been successful. On the contrary, enzyme-catalyzed synthesis of acyl-amino acids is still an important challenge worth facing. Several examples of enzymatic acylation of amino acids are discussed next. 

The synthesis of a series of thioesters of thiocarbamic acid for use in a study on the acylation of proteins has been reported. /3-Keto-thioesters have been employed in the construction of fused and bridged ring systems with a functionalized substituent in the angular position. ... 

Covalent modification of proteins is a more recently discovered role of fatty acids. Fatty acylation of proteins frequently serves as a means of targeting or anchoring a protein to a membrane. Myristoyla-tion, the addition of 14 0 to a protein, occurs at N-terminal glycine residues after removal of the initiator methionine. This process is generally co-translational and irreversible. N-myristoyl proteins include many signal-transduction-associated proteins, e.g., src and ADP-ribosylation factors. The enzyme N-myristoyltransferase catalyzes the reaction and uses 14 0-CoA as substrate. 

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