SN2-like transition for methyl transfer catalyzed by catechol-O-methyltransferase

Hegazi, Mohamed F.; Borchard, R T; Schowen, Richard L.

doi:10.1021/ja00426a079

Cited by 35 publications

(23 citation statements)

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“…Application of isotope effects as a test of this mechanism may be especially difficult in the case of complex enzyme systems such as RNA and DNA methylases. I t is therefore of considerable interest that Hegazi et al have reported a secondary isotope effect of 0.832 f 0.045 for the catechol-0-methyltransferax-catalyzed methylation of 3,4dihydroxyacetophenone by S-adenosylmethionine, trideuterated a t the transferring methyl group (182). The large inverse alpha effect is consistent with a rate-limiting 5"-2 methyl transfer:…”

Section: Catechol-0-methyltransferasementioning

confidence: 89%

Kinetic Isotope Effects in Enzymology

Klinman

1978

Advances in Enzymology - And Related Areas of Molecular Biology

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Section: Catechol-0-methyltransferasementioning

confidence: 89%

Kinetic Isotope Effects in Enzymology

Klinman

1978

Advances in Enzymology - And Related Areas of Molecular Biology

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“…All transfer reactions examined so far resulted in an inversion of the conformation at the migrating carbon. Therefore, a direct transfer of the methyl group from AdoMet to the acceptor substrate via an SN2-like transition state appears to be involved [37,38].…”

Section: Discussionmentioning

confidence: 99%

Purification, characterization, and kinetic mechanism of S‐adenosyl‐l‐methionine: vitexin 2″‐O‐rhamnoside 7‐O‐methyltransferase of Avena sativa L

Knogge

Weissenböck

1984

European Journal of Biochemistry

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An 0-methyltransferase catalyzing the transfer of the methyl group of S-adenosyl-L-methionine to the A-ring 7-hydroxyl group of vitexin 2"-O-rhamnoside has been isolated from oat primary leaves and purified 180-fold by protein fractionation with (NH,),S04 and chromatography on DEAE-cellulose and S-adenosyl-L-homocysteinesepharose. K, values for S-adenosyl-L-methionine and the flavonoid substrate were 1.6 pM and 15 pM, respectively. The lack of methyl transfer to biosynthetic intermediates suggests that the reaction is the last step in the biosynthetic pathway to the oat flavonoid 7-0-methylvitexin 2"-0-rhamnoside. Based on results obtained from kinetic inhibition studies and affinity chromatography a mono-iso Theorell-Chance mechanism is proposed with the nucleotide substrate binding before the flavonoid.Methylation of high and low-molecular-mass substances is a very abundant reaction in animal and plant tissues. The reversible covalent modification of proteins by methyltransfer via S-adenosyl-L-methionine as well as the methylation of DNA and RNAs are discussed as possible tools in cellular regulation [l -31. In plants methyl groups are very common substituents of secondary products. Several N-methyltransferases participate in alkaloid biosynthesis [4]. 0-Methyltransferases are involved in the biosynthesis of plant phenolics [5]. Particularly, numerous flavonoids are known which possess methoxyl groups at different positions of the A and B rings as well as in the 3 position of the heterocycle.Oat is frequently used as test object both in plant physiology and pathology. Several physiological reponses of the plant to light as well as one of the photoreceptors, the phytochrome system, are well known [6,7]. On the other hand, this plant is intensively investigated in the context of its rust diseases [8]. For both fields of research flavonoid biosynthesis could be of special interest.Flavonoids in general are suggested to have a function in the protection of plants against ultraviolet light [9]. Their biosynthesis, at least in part, is photo-controlled [lo]. In oat primary leaves three major flavonoid compounds accumulate : an isovitexin derivative and two structurally related vitexin derivatives one of which is methylated at the 7-hydroxyl group [Ill (Fig. 1). The latter is suggested to be a preformed antifungal substance [8].Whereas several enzymes have been isolated which catalyze the methyl transfer to the 3' position of 3',4'-dihydroxyflavonoids or to the 3 position of flavonols, only very few reports exist on para-methylation of B-ring (4') monoAbbreviations. MVR, 7-0-methylvitexin 2"-0-rhamnoside; VR, vitexin 2"-0-rhamnoside; AdoMet, S-adenosyl-L-methionine; AdoHcy, S-adenosyl-r -homocysteine; TLC, thin-layer chromatography.Enzyme. Flavonoid 0-methyltransferdse, AdoMet : vitexin 2"-0-rhamnoside 7-0-methyltransferase (EC 2.1.1 .-), R2= C-Glc-0-Rha, R3 = H : 7-0-methylvitexin 2-0-rhamnoside (MVR) ; R, = R2 = R3 = H : apigenin, R, = R, = H, R, = C-Glc : vitexin; R1 =CH3, R,=C-Glc, R,=H: 7-0-methylvitexin; R, ...

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“…The methyl-transfer reaction generally undergoes an S N 2-like mechanism and involves a ternary complex formation. 6–9 …”

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confidence: 99%

Facile synthesis of SAM–peptide conjugates through alkyl linkers targeting protein N-terminal methyltransferase 1

Zhang

Huang

2016

RSC Adv.

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SN2-like transition for methyl transfer catalyzed by catechol-O-methyltransferase

Cited by 35 publications

References 1 publication

Kinetic Isotope Effects in Enzymology

Kinetic Isotope Effects in Enzymology

Purification, characterization, and kinetic mechanism of S‐adenosyl‐l‐methionine: vitexin 2″‐O‐rhamnoside 7‐O‐methyltransferase of Avena sativa L

Facile synthesis of SAM–peptide conjugates through alkyl linkers targeting protein N-terminal methyltransferase 1

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