S-Adenosylmethionine synthetase

Dwivedi RS, Wang LJ, Mirkin BL (1999) S-adenosylmethionine synthetase is overexpressed in murine neuroblastoma cells resistant to nudeoside analogue inhibitors of S-adenosylhomocysteine hydrolase a novel mechanism of drug resistance. Cancer Res 56 1852-1856... 

K. Shimizu, I. Maruyama, S. Iijima and K. Tsukada (1986). Tripolyphosphatase associated with S-adenosylmethionine synthetase isozymes from rat liver. Biochim. Biophys. Acta, 883, 293-298. 

Takusagawa F, Kamitori S, Markham GD. Structure and function of S-adenosylmethionine synthetase crystal structures of S-adenosylmethionine synthetase with ADP, BrADP, and PPi at 2.8 angstroms resolution. Biochemistry 1996 35 2586-2596. 

In a classic paper, Snapper synthesized an ilimaquinone-agarose-affinity resin (30), which was incubated with homogenized bovine liver and then washed extensively.93 Proteins retained by the resin were separated by gel electrophoresis, yielding six main protein bands. Amino acid sequencing of these bands revealed three proteins involved in the activated methyl cycle — SAHase, S-adenosylmethionine synthetase (SAM synthetase), and catechol-O-methyltransferase (COMT) — as well as three unrelated proteins. Subsequent enzymatic assays established that ilimaquinone is a competitive inhibitor of SAHase, but has little effect on the activity of SAM synthetase or COMT. The authors noted that a consequence of SAHase inhibition would be the intracellular accumulation of SAH, which is a potent feedback inhibitor of methyltransferases. These results support the assertion that methylation events play an important role in cellular secretory events and vesicle-mediated processes. The study also highlighted the problem of nonspecific interactions as only one of the six isolated proteins was shown to interact in any way with the natural product. 

Yarlett, N., Garofalo, J., Goldberg, B. et al. (1993) S-Adenosylmethionine synthetase in bloodstream Trypanosoma brucei. Biochim. Biophys. Acta 1181 68-76. 

The natural form is the L-(+)-isomer. Due to the asymmetry of the sulfonium group, there are 4 stereoisomers. SAM is unstable at room temperature, both as a solid and in aqueous solution. It is synthesized in the cell by transfer of the adenosine residue of ATP to L-methionine Met + ATP -> SAM + PPi + P. When SAM donates a methyl group it is converted into 5-adenosyl-L-homocysteine, which is then cleaved to adenosine and L-homocysteine. The latter is remethylated to L-Methionine (see). [F. Takusagawa et al. Crystal Structure of S-Adenosylmethionine Synthetase J. Biol. Chem. 271 (1996) 13 147]... 

DL-Met is prepared on the industrial scale (more than 100,000 tons annually) by a Strecker synthesis, using P-methylmercaptopropionaldehyde prepared from acrolein and methylmercaptan. nt-Met is used to supplement poltry feed. Both d- and L-forms are effective, so that no prior separation of enantiomers is necessary. [F.Takusagawa et al. Crystal Structure of S-Adenosylmethionine Synthetase / BioL Chem. 271 (1996) 136-147]... 

Enzymatic properties of S-adenosylmethionine synthetase from the archaeon Methanococcus jannaschii. J. Biol. Chem., 277, 16624-16631. 

Because of its role in activating methionine for transmethylation, this enzyme was initially called the methionine-activating enzyme. With the later discovery of enzymes which activate the carboxyl group of methionine and other amino acids for protein synthesis, this term became somewhat confusing. In this chapter, the trivial name methionine adenosyltransferase or adenosyhransferase, will be used in accord with the recommendation of the Commission on Enzymes (Enzyme Nomenclature, American Elsevier, New York, 1965). The enzyme has also been called S-adenosylmethionine synthetase. 

Luo Y Yuan Z, Luo G, Zhao F (2008) Expression of secreted His-tagged S-adenosylmethionine synthetase in the methylotrophic yeast Pichia pastoris and its characterization, one-step purification, and immobilization. Biotechnol Prog 24 214-220 Mato JM, Pajares MA, Mingorance J, and Avarez L (1995) Production of S-adenosylmethionine (SAM) by fermentation of transformed bacteria. European Patent, vol 0647712A1, edited by E. P. Office. 

The microarray data obtained from plant tissues with altered PA levels support the contention that the biogenic amines alter ethylene response by modulating expression of ethylene signaling pathway components (Fig. 22.1). Transcriptome data indicate a potential of PAs to increase ethylene production by enhancing expression of ACS. The expression of S-Adenosylmethionine Synthetase (MAT) and Mitogen-Activated Protein Kinase Kinase (MAPKK) were also upregulated in high... 

Many NRPs such as cyclosporin, complestatin, actinomycin, and chondramide contain N-methyl amides. M-Methyl transferase (N-MT) domains utilize S-adenosylmethionine (SAM) as a cofactor to catalyze the transfer of the methyl group from SAM to the a-amine of an aminoacyl-S-PCP substrate. The presence of M-methylamides in NRPs is believed to protect the peptide from proteolysis. Interestingly, N-MT domains are incorporated into the A domains of C-A-MT-PCP modules, between two of the core motifs (A8 and A9). MT domains contain three sequence motifs important for catalysis. ° 0-Methyl transferase domains are also found in NRPSs and likewise use the SAM cofactor. For instance, cryptophycin and anabaenopeptilide synthetases contain 0-MT domains for the methylation of tyrosine side chains. These 0-MT domains lack one of the three core motifs described for N-MT domains. ... 

Secondly, adenosylmethionine synthetase, in addition to synthetase reaction, catalyses tripolyphosphatase reactions stimulated by adenosylmethionine. Both of the enzymatic activities of the enzyme, which has been purified to homogeneity from E. coli, require a divalent metal ion and are markedly stimulated by certain monovalent cations (Markham et al, 1980). Tripolyphosphatase activity is also associated with S-ade nosy I methionine synthetase isozymes from rat liver (Shimizu et al, 1986). 

Demyelination is because of failure of the methylation of arginine of myelin basic protein. The nervous system is especially vulnerable to depletion of S-adenosylmethionine in vitamin B12 deficiency because, unlike other tissues, it contains only methionine synthetase, which is vitamin B12-dependent and not vitamin B12-independent homocysteine methyl transferase that uses betaine as the methyl donor (Section 10.3.4 Weir and Scott, 1995). 

Fig. 11. Reaction scheme for (I) substrate amino acid activations and dipeptide formation, (II) racemization, and (III) N-methylation. J and E2 are symbols for enzyme activities (from peptide synthetase modules) either on the same or separate proteins. R1 and R2 are amino acid side chains, where R1 is part of the first amino acid activated by the peptide synthetase indicates the linkage between 4 -phosphopantetheinylated enzyme and the substrate or peptide intermediate. AdoMet, S-adenosylmethionine AdoHcy, S-adenosylhomocysteine...

Comprehensive Biological Catalysis—a Mechanistic Reference Volume has recently been published. The fiiU contents list (approximate number of references in parentheses) is as follows S-adenosylmethionine-dependent methyltransferases (110) prenyl transfer and the enzymes of terpenoid and steroid biosynthesis (330) glycosyl transfer (800) mechanism of folate-requiring enzymes in one-carbon metabohsm (260) hydride and alkyl group shifts in the reactions of aldehydes and ketones (150) phosphoenolpyruvate as an electrophile carboxyvinyl transfer reactions (140) physical organic chemistry of acyl transfer reactions (220) catalytic mechanisms of the aspartic proteinases (90) the serine proteinases (135) cysteine proteinases (350) zinc proteinases (200) esterases and lipases (160) reactions of carbon at the carbon dioxide level of oxidation (390) transfer of the POj group (230) phosphate diesterases and triesterases (160) ribozymes (70) catalysis of tRNA aminoacylation by class I and class II aminoacyl-tRNA synthetases (220) thio-disulfide exchange of divalent sulfirr (150) and sulfotransferases (50). 

Several of the enzymes which catalyze the interconversion of the 114-folate coenzymes are inhibited or repressed by purine nucleotides. Thus, 5,10-methylene H4-folate dehydrogenase is inhibited by ATP, GTP, and ITP (66), and 5,10-methylene H4-folate reductase is inhibited by S-adenosylmethionine (67). 10-Formyl H4-folate synthetase is repressed in cells grown in the presence of purines (68). 

Methionine adenosyltransferase 2 S-adenosylmethionine-dependent methyltransferases 3 1-aminocyclopropanecarboxylic acid (ACC) synthetase 4 oxygenase... 

Madison, J. T., and Thompson, J. F., 1976, Threonine synthetase from higher plants stimulation by S-adenosylmethionine and inhibition by cysteine, Biochem. Biophys. Res. Commun., 71 684. 

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