Methyltransferases adenosylmethionine-dependent

Fig. 6. Distribution of the most common folds in selected bacterial, archaeal, and eukaryotic proteomes. The vertical axis shows the fraction of all predicted folds in the respective proteome. Fold name abbreviations FAD/NAD, FAD/NAD(P)-binding Rossman-like domains TIM, TIM-barrel domains SAM-MTR, S-adenosylmethionine-dependent methyltransferases PK, serine-threonine protein kinases PP-Loop, ATP pyrophosphatases. mge, Mycoplasma genitalium rpr, Rickettsiaprowazekii hh x, Borrelia burgdorferi ctr, Chlamydia trachomatis hpy, Helicobacter pylori tma, Thermotoga maritima ssp, Synechocystis sp. mtu, Mycobacterium tuberculosis eco, Escherichia coli mja, Methanococcus jannaschii pho, Pyrococcus horikoshii see, Saccharomyces cerevisiae, cel, Caenorhabditis elegans.

Clarke S, Banfield (2001) S-adenosylmethionine-dependent methyltransferases. In Carmel R, Jacobsen D (eds) Homocysteine in Health and Disease. Cambridge University Press, Cambridge UK, pp 63-78... 

S-adenosylmethionine-dependent methyltransferases suggest a common structure for these enzymes. Arch Biochem Biophys 310 417-427, 1994. 

KAGAN, R. M., CLARKE, S., Widespread occurrence of 3 sequence motifs in diverse S- Adenosylmethionine-dependent methyltransferases suggests a common structure for these enzymes., Arch. Biochem. Biophys., 1994,310,417-427. 

Cheng X, Blumenthal RM, eds. S-Adenosylmethionine-dependent methyltransferases structures and functions. 1999. World Scientific, Singapore. 

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). 

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

Pyridoxalphosphate-dependent enzyme 2 adenosylmethionine-dependent methyltransferase... 

Cheng, X. and Blumenthal, R.M. (eds) (1999) S-Adenosylmethionine-Dependent Methyltransferases Structures and Functions, World Scientific, Singapore, New Jersey, London, Hong Kong. 

Takusagawa F, Fujioka M, Spies A, Schowen RL (1998) S-adenosylmethionine (adomet)-dependent methyltransferases. In Sinnott M., (ed), Comprehensive biological catalysis a mechanistic reference. Academic Press, San Diego, pp 1-30... 

The best characterized B 12-dependent methyltransferases is methionine synthase (Figure 15.11) from E. coli, which catalyses the transfer of a methyl group from methyltetrahydrofolate to homocysteine to form methionine and tetrahydrofolate. During the catalytic cycle, B12 cycles between CH3-Co(in) and Co(I). However, from time to time, Co(I) undergoes oxidative inactivation to Co(II), which requires reductive activation. During this process, the methyl donor is S-adenosylmethionine (AdoMet) and the electron donor is flavodoxin (Fid) in E. coli, or methionine synthase reductase (MSR) in humans. Methionine synthase... 

As shown in Figure 8.3, the principal metabolites of nicotinamide are A( -methyl nicotinamide and methyl pyridone carboxamides. AT -Methyl nicotinamide is actively secreted into the urine by the proximal renal tubules. Nicotinamide A(-methyltransferase is an S-adenosylmethionine-dependent enzyme that is present in most tissues. Very high intakes of nicotinamide may deplete tissue pools of one-carbon fragments - indeed, this was the basis for the use of nicotinamide in the treatment of schizophrenia (Section 8.8). 

Putrescine N-methyltransferase Atropa belladonna S-adenosylmethionine-dependent N-methyltrantfsrase a< SE... 

Scoulerine 9-0-methyltransferase Coptis Japonica S-adenosylmethionine-dependent 0-methyltransferaae ao—E... 

Fig. 20.3 Pathway of methionine metabolism. The numbers represent the following enzymes or sequences (1) methionine adenosyltransferase (2) S-adenosylmethionine-dependent transmethylation reactions (3) glycine methyltransferase (4) S-adenosylhomocysteine hydrolase (5) betaine-homocysteine methyltransferase (6) 5-methyltetrahydrofolate homocysteine methyltransferase (7) serine hydroxymethyltransferase (8) 5,10-methylenetetrahydrofolate reductase (9) S-adenosylmethionine decarboxylase (10) spermidine and spermine synthases (11) methylthio-adenosine phosphorylase (12) conversion of methylthioribose to methionine (13) cystathionine P-synthase (14) cystathionine y-lyase (15) cysteine dioxygenase (16) cysteine suplhinate decarboxylase (17) hypotaurine NAD oxidoreductase (18) cysteine sulphintite a-oxoglutarate aminotransferase (19) sulfine oxidase. MeCbl = methylcobalamin PLP = pyridoxal phosphate...

The methylation also required a small amount of S-adenosylmethionine (AdoMet) its competitive inhibitor, adenosylhomocysteine, when added to the incubation mixture in the presence of CHaCbl, blocked the transfer of methyl groups to DNA. Furthermore, it appears that methylases of Bn and Bi2-deficient cells might use different donors of CHs-groups. The methylase of vitamin Bi 2-deficient cells showed a higher affinity for AdoMet and catalyzed efficiently the methylation of both cytosine and adenine. The methylase of B " cells methylated adenine, but not cytosine with AdoMet. It is possible that AdoMet is used in the absence of CHaCbl as the natural donor of CH3 groups for DNA methylation. In the presence of CHsCbl, additional methylation is specifically catalyzed by a vitamin B -dependent methyltransferase. It seems likely that either there are two separate methylases or one enzyme with two coenzyme sites, one binding AdoMet, and another CHsCbl... 

Figure 11.6. Schematic diagram of the possible sites of action of drugs that modify dopaminergic function in striatal and other non-mesocortical regions of the mammalian brain. PCM=protein 0-methyltransferase, which catalyses the transfer of methyl groups from S-adenosylmethionine to the calmodulin-dependent regulatory protein and may regulate calcium-calmodulin dependent transmitter synthesis and release. (—)=inhibition (+)=stimulation DA=dopamine. Sites of action of drugs are underlined.

Highly populated protein domain families of H. pylori include (1) the cellular component Helicobacter outer membrane protein family (2) the sell family, which is associated with P-lactamase activity (3) members of the CagA and VacA protein families, which are secreted into host cells and are involved in pathogenesis (4) the ABC transporter family, which is associated with ATP-dependent transport of molecules across the membrane (5) the DNA methyltransferase protein domain family (6) the radical SAM (S-adenosylmethionine) family associated with various metabolic functions of pathogens and (7) the response regulator receiver domain family, which is involved in receiving the signal from the sensor domain in bacterial two-component systems. 

Fig. 4. Polyketide biosynthesis by gene products of the act PKS cluster. Presence of the KS/AT, CLF, and ACP is sufficient for the production of two 16-carbon polyketides, SEK4 and SEK4b both in vivo [ 103] and in vitro [107]. In the presence of the act ketoreductase (KR), aromatase (ARO) and cyclase (CYC), the octaketide intermediate is converted into DMAC. DMAC can be converted into 8-methoxy DMAC both in vivo and in vitro through the S-adenosylmethionine (Adomet)-dependent action of the tcmO methyltransferase [207]...

The additional presence of phenylethanolamine N-methyltransferase in adrenal medullary chromaffin cells leads to further conversion of norepinephrine to epinephrine (Figure 29-2). Since phenylethanolamine N-methyitransferase is a cytosolic enzyme, this step depends on leakage of norepinephrine from vesicular storage granules into the ceU cytoplasm and the transfer of a methyl group from S-adenosylmethionine to norepinephrine. Epinephrine is then translocated into chromaffin granules where the amine is stored, awaiting release. 

Methylation is the addition of a carbon atom to a molecule, usually causing a change in the function of the methylated molecule. For example, methylation of the neurotransmitter dopamine by catechol-O-methyltransferase renders it inactive. With only two exceptions, 5-adenosylmethionine (SAM), an activated form of the essential amino acid methionine, is the methyl donor for each of the more than 150 methylation reactions, which regulate a large number of cellular functions. One exception is methylation of homocysteine (HCY) to methionine by the cobalamin (vitamin Bi2)-dependent enzyme methionine synthase, which utilizes 5-methyltetrahydrofolate (methylfolate) as the methyl donor, serving to complete the methionine cycle of methylation, as illustrated in Fig. 1 (lower right). Notably, HCY formation from S-adenosylhomocysteine (SAH) is reversible and, as a result, any decrease in methionine synthase activity will be reflected as an increase in both HCY and SAH. This is significant because SAH interferes with SAM-dependent methylation reactions, and a decrease in methionine synthase activity will decrease all of these reactions. Clearly methionine synthase exerts a powerful influence over cell function via its control over methylation. 

Of the substrates for the betaine and thetin methyltransferases, only betaine is formed in the liver. Dimethylpropiothetin and S-methylme-thionine also occur naturally, but are formed only in plants and algae (Cantoni, 1960). It appears that, physiologically, betaine is the chief methyl donor for these enzymes in mammalian tissues with, perhaps, minor utilization of such S-methylmethionine or thetins as may be ingested in foods derived from plant material. Betaine is formed by oxidation of choline. Choline is formed by a series of transmethylations, each of which utilizes a molecule of S-adenosylmethionine. Clearly, therefore, the betaine-dependent pathway does not provide the animal with a means of... 

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