AdoMet-dependent methyltransferase

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... 

S ETdomain containing H KMTs have been classified according to the presence or absence and the nature of the sequences surrounding the SET domain that are conserved within families [71, 72]. The SET domain has a unique structural fold classified as class V AdoMet-dependent methyltransferase (MTase) [69], characterized by four highly-conserved signature sequences, namely motif I... 

The metabolic control of methionine metabolism is complex and involves, for example, changes of enzyme levels in particular tissues, mechanisms linked to the kinetic properties of the various enzymes and their interaction with metabolic effectors [6, 7]. A particularly important metabolic effector is AdoMet. This inhibits the low Km isoenzymes of MAT, and MTHF reductase, inactivates betaine methyltransferase, but activates MAT III (the high-Km isoenzyme) and cystathionine /1-synthase. Therefore, high methionine intake and thus higher AdoMet levels favour trans-sulphuration, and when levels are low methionine is conserved. AdoHcy potently inhibits AdoMet-dependent methyltransferases and both Hey remethylating enzymes. Another important control mechanism is the export of Hey from cells into the extracellular space and plasma, which occurs as soon as intracellular levels increase [8]. 

AdoMet-Dependent Methyltransferases, Chemistry of DNA, Covalent Modifications of Histone Acetyltransferases, Selective Inhibitors of Post-Translational Modifications to Regulate Protein Eunction... 

A swap of the methyl carbon with nitrogen in aza-AdoMet leads to sinefungin (see Fig. 2g)—a natural nucleoside antibiotic found in Streptomyces griseolus. Such reverse chemistry additionally enhances the chemical stability of cofactor. Because of the positive charge of the protonated amine and correct chirahty at the carbon center, sinefungin has an extremely high inhibitory potential for AdoMet-dependent methyltransferases. 

Klimasauskas S, Weinhold E. A new tool for biotechnology AdoMet-dependent methyltransferases. Trends Biotechnol. 2007 25 99-104. 

The available information on 5-methylmethionine does not provide convincing indication of a physiological role for this compound. If there is any methylated metabolite the formation of which occurs only through utilization of 5-methylmethionine as methyl donor, that fact has yet to be discovered. For the moment, plant methyltransferases appear to conform to the generalization that for an enzymatic methyl transfer to a compound other than homocysteine, AdoMet is the methyl donor (Mudd and Cantoni, 1%4 Canton , 1977). Although 5-methylmethionine has been tested as a methyl donor with only a minority of the reported plant AdoMet-dependent methyltransferases, in those cases in which it has been tried it has been inactive (Mudd, l%0b Mann et al., 1963). 

Schluckebier, G., O Gara, M., Saenger, W. Cheng, X. Universal catalytic domain structure of AdoMet-dependent methyltransferases. Journal of Molecular Biology 247, 16-20 (1995). 

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