Methyltransferases carboxyl methyl

Figure 19-5 Schematic representation of an important chemotactic system of E. coli, S. typhimurium, and other bacteria. The transmembrane receptor activates the autokinase CheA, which transfers its phospho group to proteins CheY and CheB to form CheY-P and CheB-P. CheY-P regulates the direction of rotation of the flagella, which are distributed over the bacterial surface. CheR is a methyltransferase which methylates glutamate carboxyl groups in the receptor and modulates the CheA activity. CheZ is a phosphatase and CheB-P a methylesterase.

A number of proteins such as histones, cytochrome c and certain flagellar proteins are found to contain methylated amino acids (19). Three different methylases have been characterized and all require S-adenosylmethionine (SAM) as the methyl donor (20-23). Protein methylase I (SAM-protein arginine methyl transferase) methylates the guanidine side chain of arginine residue protein methylase II (SAM-protein carboxyl methyltransferase) transfers methyl groups only to 8- and y-carboxyl groups in the peptide chain. Carboxyl groups in the a position cannot serve as acceptors. Protein methylase III (SAM-protein lysine... 

Lu, Q., et al. (2004). Isoprenylcysteine carboxyl methyltransferase modulates endothelial monolayer permeabihty involvement of Rho A carboxyl methylation. Circ Res 94 306-315. 

The first evidence for the existence of the methylation of a prenylated peptidyl substrate was found in two jelly fungi, Tremella mesenterica and Tremella brasiliensis [30,31]. These peptide sequences are similar to the a-mating factor found in Saccharomyces cerevisiae, which is also prenylated at the C-terminus and contains an a-carboxyl methyl ester [32]. The gene product of the STEM in S. cerevisiae was found to be responsible for the methylation event for the a-factor-mating pheromone and the enzymatic activity of this methyltransferase was found only in the cellular membrane fractions [33,34]. Further analyses of Stel4p via epitope tagging determined that the enzyme is localized to the ER membrane and possesses six transmembrane segments, with majority of the enzyme exposed to the cytosol [35,36]. 

The proposed biosynthetic pathway of A-503083B (39) is reported in the Figure 7.12. Cap W, a putative class C p-lactamase, was thought to be involved in the formation of the amide bond between L-amino-caprolactam and the methyl ester moiety as the ultimate step of the biosynthesis of 39. Cap S and Cap K are two putative methyltransferases (carboxyl-methyltransferse and O-methylttansferase, respectively), whereas Cap B is a carbamoyltransferase. Cap U and likely Cap V are required for L-amino-caprolactam formation [24]. 

Trace Amines. Figure 1 The main routes of trace amine metabolism. The trace amines (3-phenylethylamine (PEA), p-tyramine (TYR), octopamine (OCT) and tryptamine (TRP), highlighted by white shading, are each generated from their respective precursor amino acids by decarboxylation. They are rapidly metabolized by monoamine oxidase (MAO) to the pharmacologically inactive carboxylic acids. To a limited extent trace amines are also A/-methylated to the corresponding secondary amines which are believed to be pharmacologically active. Abbreviations AADC, aromatic amino acid decarboxylase DBH, dopamine b-hydroxylase NMT, nonspecific A/-methyltransferase PNMT, phenylethanolamine A/-methyltransferase TH, tyrosine hydroxylase. 

Phenazines — The phenazines are biosynthesized by the shikimic acid pathway, through the intermediate chorismic acid. The process was studied using different strains of Pseudomonas species, the major producers of phenazines. The best-known phenazine, pyocyanine, seems to be produced from the intermediate phenazine-1-carboxylic acid (PCA). Although intensive biochemical studies were done, not all the details and the intermediates of conversion of chorismic acid to PCA are known. In the first step, PCA is N-methylated by a SAM-dependent methyltransferase. The second step is a hydroxylative decarboxylation catalyzed by a flavoprotein monooxygenase dependent on NADH. PCA is also the precursor of phenazine-1-carboxamide and 1-hydroxyphenazine from Pseudomonas species. - - ... 

Brossi, A. 1991. Mammalian alkaloids Conversion of tetrahydroisoquinoline-1-carboxylic acids derived from Dopamine. Planta Medica, 57 S93-S100 and, Xe, X. S., Tadic, D Brzostowska, M Brossi, A., Bell, M. and Creveling, C. 1991. Mammalian alkaloids - Synthesis and O-methylation of (S)-3 -hydroxycoclaurine and R-3 -hydroxycoclaurine and their N-methylated analogs with S-adenosyl-L-[methyl-C-14]methionine in presence of mammalian catechol O-methyltransferase. Helvetica Chimica Acta, 74 1399-1411. 

Aswad DW. Stoichiometric methylation of porcine adrenocorticotropin by protein carboxyl methyltransferase requires deamidation of asparagine 25. Evidence for methylation at the alpha-carboxyl group of atypical L-isoaspartyl residues. J Biol Chem 1984 259 10714-10721. 

A third group of OMTs are the protein carboxyl MTs, whose molecular mass is approximately 27 kDa 43 These proteins are found in almost all organisms, and they serve to repair damaged proteins. In plants, they have been shown to be important during stress and in seed viability.14. Their sequences are related to the animal glycine N-methyltransferases (NMTs) and die RNA/DNA MTs. Furthermore, the plant protein carboxyl MTs share no similarity to the other plant MTs involved in specialized metabolism. The enzyme that methylates a carboxyl functionality of Mg-protoporphyrin IX to produce a methylester constitutes a fourth type of plant OMT. This chloroplastic protein, whose mature form has a molecular mass of 31 kDa, is related to MTs with similar functions from photosynthetic bacteria, but is not closely related to any other plant OMTs.6... 

MURFITT, L. M., KOLOSOVA, N., MANN, C. J., DUDAREVA, N Purification and characterization of S-adenosyl-L-methionine Benzoic acid carboxyl methyltransferase, the enzyme responsible for biosynthesis of the volatile ester methyl benzoate in flowers of Antirrhinum majus., Arch Biochem. Biophys., 2000, 382,145-151. 

The first evidence for this modification in mammalian cells was obtained when human Ha-Ras was transfected into rat fibroblasts and was found to be methylated at a C-terminal prenylated cysteine [38]. Based on the previous studies in yeast and jelly fungi, it was suggested this occurred by a third class of methyltransferase. Although Ras proteins have httle structural and sequence similarity to the fungi and yeast peptide substrates, they all have a unique characteristic a prenylated cysteine residue at the carboxyl terminus. The authors thus proposed that this motif is responsible for the recognition of this new class of methyltransf erase. 

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