Disease relevance of Acylation

• Activation of Escherichia coli prohaemolysin to the mature toxin by acyl carrier protein-dependent fatty acylation [1].
• The results show that chitin oligosaccharides are much better substrates than LCOs, suggesting that in Rhizobium NodZ fucosylates chitin oligosaccharides prior to their acylation [2].
• Membrane interactions of simian virus 40 large T-antigen: influence of protein sequences and fatty acid acylation [3].
• The microsomal fraction of M1 cells (an established cell line of myeloid leukemia) was capable of catalyzing acylation of sn-glycerol 3-phosphate by long-chain fatty acyl-CoA thioesters [4].
• To sort out possible influences of protein sequences and fatty acid acylation on the plasma membrane association of simian virus 40 large T-antigen, we have analyzed the membrane interactions of carboxy-terminal fragments of large T-antigen, encoded by the adenovirus type 2 (Ad2+)-simian virus 40 hybrid viruses Ad2+ND1 and Ad2+ND2 [3].

High impact information on Acylation

• The AGPAT2 enzyme catalyzes the acylation of lysophosphatidic acid to form phosphatidic acid, a key intermediate in the biosynthesis of triacylglycerol and glycerophospholipids [5].
• Mutations in SUPH-STE16 prevent the membrane localization and maturation of RAS protein, as well as the fatty acid acylation of it and other membrane proteins [6].
• These amide aminoacyl-tRNAs can be formed by the direct acylation of tRNA, catalysed by asparaginyl-tRNA synthetase and glutaminyl-tRNA synthetase, respectively [7].
• In addition, we show that exposure to nitric oxide inhibits thioester-linked long-chain fatty acylation of neuronal proteins, possibly through a direct modification of substrate cysteine thiols [8].
• Surprisingly, this partition of aaRS in two classes is found to be strongly correlated on the functional level with the acylation occurring either on the 2' OH (class I) or 3' OH (class II) of the ribose of the last nucleotide of tRNA [9].

Chemical compound and disease context of Acylation

• When 100-120 micrograms of disuccinimidyl suberate was used in the 18F-labeled acylation agent synthesis, the binding of 18F-labeled Mel-14 F(ab')2 to glioma homogenates was comparable to that of the radioiodinated fragment [10].
• The exact nature of this modification is unknown, but homology to the related repeat toxin alpha-hemolysin of Escherichia coli suggests that fatty acylation of a lysine residue may be involved [11].
• Role of fatty acid acylation of membrane glycoproteins. Absence of palmitic acid in glycoproteins of two serotypes of vesicular stomatitis virus [12].
• Cell-free fatty acylation of microsomal integrated and detergent-solubilized glycoprotein of vesicular stomatitis virus [13].
• Cerulenin blocks fatty acid acylation of glycoproteins and inhibits vesicular stomatitis and Sindbis virus particle formation [14].

Biological context of Acylation

• Here we propose two possible mechanisms for LPS recognition and signalling that take into account both the structural information available for TLR4 and MD-2, and the determinants of endotoxicity, namely, the acylation and phosphorylation patterns of LPS [15].
• We show here that ongoing fatty acylation can be inhibited selectively by long-chain homologues of the antibiotic tunicamycin, a known inhibitor of N-linked glycosylation [16].
• The endosomal localization of Ara6 requires N-terminal fatty acylation, nucleotide binding and the C-terminal amino acid sequence coordinately [17].
• We show that TIP1 binds the acyl group palmitate, that it can rescue the morphological, temperature sensitivity, and yeast casein kinase2 localization defects of the yeast S-acyl transferase mutant akr1Delta, and that inhibition of acylation in wild-type Arabidopsis roots reproduces the Tip1- mutant phenotype [18].
• In hyperapoB cells, BP II markedly increased (up to 9-fold) the incorporation of [14C]oleate into cholesteryl ester compared with that in normal cells; in addition, there was a 50% decrease in the stimulation of triglyceride acylation and cholesterol esterification with BP I [19].

Anatomical context of Acylation

• Radioimmunoprecipitates from the supernates of labeled monocytes indicated that the processed or mature 17-kD form of TNF does not contain myristate, suggesting that the site of acylation occurs within the 76-amino acid propiece of the precursor molecule [20].
• These results suggest a novel role for fatty acylation in the specific compartmentalization of eNOS and most likely, for other dually acylated proteins, to the Golgi complex [21].
• Both GlcN-(2-O-octyl)PI and GlcNAc(2-O-octyl)PI also inhibit inositol acylation of Man(1-3)GlcN-PI and, consequently, the addition of the ethanolamine phosphate bridge in the T.brucei cell-free system [22].
• Two different methods, stimulation of transport by fatty acyl-coenzyme A (CoA) and inhibition of transport by a nonhydrolyzable analogue of palmitoyl-CoA, reveal that fatty acylation is required to promote fusion of transport vesicles with Golgi cisternae [23].
• Moreover, they demonstrate that inositol acylation is required for mannosylation in the HeLa cell GPI biosynthetic pathway, whereas it is required for ethanolamine phosphate addition in the T.brucei GPI biosynthetic pathway [24].

Associations of Acylation with chemical compounds

• Acylation of proteins with myristic acid occurs cotranslationally [25].
• Amino acid acylation: a mechanism of nitrogen excretion in inborn errors of urea synthesis [26].
• Treatment of a patient deficient in carbamyl phosphate synthetase with benzoate or phenylacetic acid resulted in an increase in urinary nitrogen, which could be accounted for by the respective amino acid acylation product, hippurate or phenylacetylgultamine [26].
• A synthetic palmitoylated peptide corresponding to the tryptic fragment (glutamine 972 to arginine 984) that contained the acylation blocked AC toxin-induced accumulation of adenosine 3',5'-monophosphate, whereas the non-acylated peptide had no effect [27].
• Acylation of the purified erythromycin-producing polyketide synthase has shown that all six acyltransferase domains have identical stereospecificity for their normal substrate, (2S)-methylmalonyl-CoA [28].

Gene context of Acylation

• Acylation of the IL-1 alpha precursor by a previously unrecognized lysyl epsilon-amino N-myristoyl-transferase activity may facilitate its specific membrane targeting [29].
• For the alpha 2AAR (human alpha 2 C10) palmitoylation occurs at Cys-442, but it is not known what function such fatty acid acylation subserves [30].
• The DPR1 product has been shown to be responsible for processing and fatty acid acylation of a-factor and RAS proteins at their carboxyl termini [31].
• We examined the role of fatty acylation in the maturation of yeast RAS2 protein by creating mutants in the putative palmitate addition site located at the carboxyl terminus of the protein [32].
• Reversible acylation of eNOS is thought to contribute to the intracellular trafficking of the enzyme; however, protein factor(s) that govern the translocation of the enzyme are still unknown [33].

Analytical, diagnostic and therapeutic context of Acylation

• These results indicate that the procedure, to which we have referred as adduct detection by acylation with methionine (ADAM), has potential applicability as an analytical procedure for detection and quantification of DNA adducts in human tissues in the molecular epidemiology of cancer [34].
• Two conserved cysteine residues 417 and 420 located in the proximal C-terminal domain were identified as acylation sites by site-directed mutagenesis [35].
• Separation of platelet phospholipids and subsequent resolution into individual molecular species by high-performance liquid chromatography revealed that the newly formed alkylacyl-GPC was exclusively alkylarachidonoyl-GPC and that the arachidonoyl group for acylation of alkyllyso-GPC was provided by phosphatidylcholine [36].
• Bovine thyroglobulin is succinylated and the succinylated protein is coupled to beta-ecdysone with 1-ethyl-3-(-dimethylaminopropyl)-carbodiimide in the presence of the acylation catalyst 4-dimethylaminopyridine, The antiserum obtained using this immunogen provides a radioimmunoassay sensitive to 25 pmol of beta-ecdysone [37].
• Limited proteolysis and peptide mapping showed that the same sites on the proteolipid protein were acylated when the reaction was carried out in isolated myelin preparations or in brain tissue slices, suggesting physiological importance for the in vitro acylation of endogenous myelin proteolipid protein [38].

References