S-adenosyl-L-methionine dependent

LEUSTEK, T SMITH, M MURILLO, M., SINGH, D. P., SMITH, A. G., WOODCOCK, S. C AW AN, S. J., WARREN, M. J., Siroheme biosynthesis in higher plants - Analysis of an S- adenosyl-L-methionine-dependent uroporphyrinogen III methyltransferase from Arabidopsis thaliana., J. Biol. Chem., 1997,272,2744-2752. 

RATHINASABAPATHI, B., SIGUA, C., HO, J., GAGE, D. A., Osmoprotectant beta-alanine betaine synthesis in the Plumbaginaceae S-adenosyl-L-methionine dependent N-methylation of beta-alanine to its betaine is via N-methyl and N,N-dimethyl beta-alanines., Physiol. Plant., 2000,109,225-231. 

JOSHI, C. P., CHIANG, V. L., Conserved sequence motifs in plant S-adenosyl-L-methionine- dependent methyltransferases., Plant Mol.Biol., 1998,37,663-674. 

Vevodova J, Graham RM, Raux E, Schubert HL, Roper Dl, Brindley AA, et al. Structure/function studies on a S-adenosyl-L-methionine-dependent uroporphyrinogen 111 C methyltransferase (SUMT), a key regulatory enzyme of tetrapyrrole biosynthesis. J. Mol. Biol. 2004 344 419-433. 

Methyl transfer reactions play a significant part in the modifications of aromatic polyketides, both of the polyketide core [61,62] as well as of several of the sugar moieties [44,53]. In Streptomyces, more than 20 amino acid sequences have been found that may represent enzymes involved in methyl transfer reactions in the biosynthesis of aromatic polyketides [149]. One of these enzymes, the S-adenosyl-L-methionine-dependent DnrK, is involved in the methylation of the C-4 hydroxyl group in daunorubicin/doxorubicin biosynthesis (Scheme 10, step 12). The subunit of the homo-dimeric enzyme displays a fold typical for small-molecule methyltransferases. The structure of the ternary complex with bound products S-adenosyl-L-homocysteine and 4-methoxy-8-rhodomycin provided insights into the structural basis of substrate recognition and catalysis [149]. The position and orientation of the substrates suggest an Sn2 mechanism for methyl transfer, and mutagenesis experiments show that there is no catalytic base in the vicinity of the substrate. Rate enhancement is thus most likely due to orientational and proximity effects [149]. 

Lee, E. S., Chen, H., Hardman, C., Simm, A., and Charlton, C. (2008). Excessive S-adenosyl-1-methionine-dependent methylation increases levels of methanol, formaldehyde and formic add in rat brain striatal homogenates Possible role in S-adenosyl-l-methionone-induced Parkinsons s disease-like disorders. Life Sci. 83, 821-827. 

TGN represents the sum of 6-thioguanosine monophosphate (6-thio-GMP), -diphosphate (6-thio-GDP) and -triphosphate (6-thio-GTP). In contrast, both TPMT and XO are the predominant catabolic enzymes in the metabolism of thiopurines. TPMT catalyses the X-adenosyl-L-methionine dependent S-methylation of 6-MP and its metabolites into 6-methyl-mercaptopurine (6-MMP), 6-methyl-mercaptopurine ribonucleotides (6-MMPR) such as 6-methylthioinosine monophosphat (meTIMP), and 6-methyl-thioguanine nucleotides (6-MTGN) (93). 

Calmodulin-dependent phosphodiesterase = Dibutyryl cyclic AMP = Acyl carrier protein = S-Adenosyl-L-methionine = S-Adenosyl-I-homocysteine... 

The most widely used methyl donor for enzymatic methyl transfer is the cofactor S-adenosyl-L-methionine (SAM). The methyl moiety on the L-methionine is supplied by another known methyl donor, N5-methyl tetrahydrofolate.30 To date, numerous enzymes that perform SAM- dependent methylation reactions have been described in plants, and several reports attempting to sort out their evolutionary relationships have been published.31- 3... 

S-adenosyl-L methionine (ADO-Met) dependent DNA methyl transferase catalyzed the transfer of a methyl group from AdoMet to a specific nucleotide within the DNA helix (Cheng et al., 1993). In a concerted reaction in the enzyme active site (Fig X) with a simultaneous addition of methyl residue of AdoMet to the cytosine ring and with an elimination of the ring proton by a water molecule requires involving seven heavy nuclei (two ofCys 81, four of AdoMet and one of water. An estimation with aid of Eq. 2.44 leads to value of the reaction synchronization factor asyn 10 4, that does not rule out the concerted mechanism, if the activation energy is less than 10 kcal/mole Nevertheless, a... 

According to the above-mentioned hypothesis, the caffeic acid moiety is retransferred to coenzyme A for further modification reactions. Methylation of the caffeoyl moiety in position 3 is achieved by S-adenosyl-L-methionine (SAM)-dependent 0-methyltransferases (OMTs) either acting on the level of the free acid or the coenzyme A thioester. Hydroxylation in position 5 is catalysed by a cytochrome P450 of the CYP84 family which will be described in more detail. Establishment of the sinapoyl substitution pattern by adding another methyl group will be depicted below. 

The crystal structure of 5-8-azaadenosyl-L-homocysteine has been examined because this substance inhibits a methyltransferase that depends on S -adenosyl-L-methionine as a cofactor. ... 

S-adenosyl-L-methionine (SAM)-dependent methyl-ation was briefly discussed under Thiomethylation (see Figure 14). Other functional groups that are methylated by this mechanism include aliphatic and aromatic amines, N-heterocyclics, monophenols, and polyphenols. The most important enzymes involved in these methylation reactions with xenobiotics are catechol O-methyltransferase, histamine N-methylt-ransferase, and indolethylamine N-methyltransferase - each catalyzes the transfer of a methyl group from SAM to phenolic or amine substrates (O- and N-methyltransferases, respectively). Methylation is not a quantitatively important metabolic pathway for xenobiotics, but it is an important pathway in the intermediary metabolism of both N- and O-contain-ing catechol and amine endobiotics. 

Borchardt, R.T., Wu, Y.S., and Wu, B.S. (1978) Potential inhibitors of S-adenosyl-methionine-dependent methyltransferases. 7. Role of the ribosyl moiety in enzymatic binding of S-adenosyl-L-homocysteine and S-adenosyl-L-methionine. J. Med. Chem. 21, 1307-1310. 

Spermidine 4 was biosynthesized from putrescine 2 (NC4N), obtained by ornithine 1, and adenosyl-L-methionine (activated C3 unit). S -Adenosyl-L-methioninamine (decarboxylated 5-adenosyl-L-methionine) donates an aminopropyl group to putrescine 2 to form spermidine 4 in a reaction catalyzed by spermidine synthase. Homospermidine 3 is formed from two moles of putrescine 2 in an NAD" -dependent reaction catalyzed by HSS. Moreover, HSS catalyzes the NADI-dependent transfer of an aminobutyl group of spermidine 4 to putrescine 2 to form homospermidine 3. 

Struck, A.-W., Thompson, M.L., Wong, L.S., and Micklefield, J. (2012) S-adenosyl-methionine-dependent methyltransferases highly versatile enzymes in biocatalysis, biosynthesis and other biotechnological applications. ChemBioChem, 13, 2642-2655. 

---