Homochiral synthesis of an aza analogue of S-adenosyl-L-methionine (AdoMet) and its binding to the E. coli methionine repressor protein (MetJ)

Thompson, Mark J.; Mekhalfia, Abdelaziz; Jakeman, David L.; Phillips, Simon E. V.; Phillips, Kathryn; Porter, Jonathan; Blackburn, G. Michael

doi:10.1039/cc9960000791

Cited by 18 publications

(15 citation statements)

References 19 publications

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“…The existence of DMAA has already been reported (Davis et al, 1983;Follman & Gremels, 1974;Minnick & Kenyon, 1988;Thompson et al, 1996;Thompson et al, 1999), with most reports related to studies of polyamine metabolism inhibitors (Davis et al, 1983;Minnick & Kenyon, 1988;Thompson et al, 1996;Thompson et al, 1999). Two analogues of DMAA, 5 -deoxy-5 -[N-methyl-N-[2-(aminooxy)ethyl]amino]adenosine (MAOEA) and 5 -deoxy-5 -[N-methyl-N-(3-hydrazinopropyl) amino]adenosine (MHZPA), were reported to inhibit S-adenosylmethionine decarboxylase (SAMDC), which is a key enzyme in polyamine metabolism; the inhibition of SAMDC by MAOEA or MHZPA increases the putrescine level and decreases spermidine and spermine content (Pegg et al, 1988).…”

Section: Discussionmentioning

confidence: 79%

Isolation and structural elucidation of a growth stimulant for arbuscular mycorrhizal fungus from Laminaria japonica Areschoug

Kuwada¹,

Kuramoto

Utamura³

et al. 2006

J Appl Phycol

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Arbuscular Mycorrhizal (AM) fungi enhance terrestrial plant growth by forming a symbiotic relationship with the roots of its host plant. A growth stimulant for AM fungi was isolated from a brown alga Laminaria japonica Areschoug. The active substance for in vitro AM hyphal growth was isolated from 75% methanol extracts of L. japonica using a succession of chromatographic procedures, including flash chromatography equipped with an octa decyl silane (ODS) column, gel filtration chromatography and HPLC using an ODS column. Spores of Gigaspora margarita Becker & Hall, an AM fungus, were exposed to the compound in vitro, and hyphal growth of G. margarita was measured after two weeks of incubation. At 40 mg L −1 , the compound significantly stimulated the in vitro hyphal growth of G. margarita, compared to the K. Kuwada ( ) · M. Utamura control. This compound was elucidated as 5 -deoxy-5 -methylamino-adenosine by EIMS and NMR spectrum.

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Section: Discussionmentioning

confidence: 79%

Isolation and structural elucidation of a growth stimulant for arbuscular mycorrhizal fungus from Laminaria japonica Areschoug

Kuwada¹,

Kuramoto

Utamura³

et al. 2006

J Appl Phycol

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“…The pK a of the tertiary amine of aza-AdoMet is reported to be 7.1 (31,34), in which case the nitrogen center would be predominantly uncharged under the conditions used here to assay Ecm1 activity, but predominantly charged under the conditions used to grow the crystals. However, it is unlikely that the relatively low inhibitory potency of aza-AdoMet is caused only by the absence of a positive charge equivalent to the AdoMet sulfonium group, because the neutral AdoHcy product is itself an effective competitor for the methyl donor site.…”

Section: Discussionmentioning

confidence: 99%

Encephalitozoon cuniculi mRNA Cap (Guanine N-7) Methyltransferase

Hausmann

Zheng

Fàbrega

et al. 2005

Journal of Biological Chemistry

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The Encephalitozoon cuniculi mRNA cap (guanine N-7) methyltransferase Ecm1 has been characterized structurally but not biochemically. Here we show that purified Ecm1 is a monomeric protein that catalyzes methyl transfer from S-adenosylmethionine (AdoMet) to GTP. The reaction is cofactor-independent and optimal at pH 7.5. Ecm1 also methylates GpppA, GDP, and dGTP but not ATP, CTP, UTP, ITP, or m The 5Ј cap of eukaryotic messenger RNA consists of 7-methyl guanosine linked via an inverted 5Ј-5Ј triphosphate bridge to the initiating nucleoside of the transcript. The cap is formed by three enzymatic reactions: (i) the 5Ј-triphosphate end of the pre-mRNA is hydrolyzed to a diphosphate by RNA 5Ј-triphosphatase; (ii) the diphosphate RNA end is capped with GMP by

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“…The chemical syntheses of AzaAdoMet (41) were started from 2 0 ,3 0 -O-isopropylidene-5 0 -O-tosyladenosine (23), which was first converted with methylamine to protected 5 0 -deoxy-5 0 -methylaminoadenosine and then 5 0 -N-alkylated with iodides of amino acid side chain precursors. After deprotection, AzaAdoMet (41) was obtained as a diastereomeric mixture at the amino acid center [147,148], and later as a single diastereoisomer [149,150]. As expected, AzaAdoMet (41) does not serve as a methyl group donor for MTases [151].…”

Section: Nitrogen Analogues Of Adometmentioning

confidence: 99%

“…Type III restriction endonucleases require the binding of AdoMet (1) for DNA cleavage, and AzaAdoMet (41) -but not AdoHcy (2) -can replace the natural cofactor to bring about a conformational change of the enzyme necessary for endonuclease activity [155]. The ternary amino group of AzaAdoMet (41) has an unusually low pK a value of about 7.1, and thus acts as a charge-switchable analogue of AdoMet [149]. This property was utilized to probe the molecular mechanism of the E. coli methionine repressor MetJ, which does not undergo any significant structural change upon AdoMet binding, yet still binds its operator DNA sequence about 100-fold tighter in the presence of AdoMet (1).…”

Section: Nitrogen Analogues Of Adometmentioning

confidence: 99%

S‐Adenosyl‐L‐Methionine and Related Compounds

Dalhoff¹,

Weinhold

2008

Modified Nucleosides

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The sulfonium compound S-adenosyl-L-methionine (AdoMet, also known as SAM or SAMe, 1) is one of the most versatile biomolecules in nature and one of the most widely used enzyme substrates, second perhaps only to adenosine triphosphate (ATP) (Schemes 9.1 and 9.2). AdoMet (1) may be found in all phyla of life, and is one of the molecules crucial for the existence of living organisms. First identified by Cantoni in 1953 [1, 2] as the active methyl donor formed from L-methionine and ATP, AdoMet (1) proved to be not only the major methyl donor in nature but also to be involved in many other metabolic reactions [3,4]. The versatility of the cofactor is based on the reactivity of the pivotal sulfonium center, which activates the adjacent carbon atoms for nucleophilic attack, deprotonation, and radical formation. This leads to a unique cofactor in which all constituents are used in biochemical reactions. The group transfer reactions result in the release of one of three different thioether products which are more stable than the sulfonium compound, and thereby providing the driving force for these enzyme-catalyzed reactions. These highly preferable thermodynamics of AdoMet-dependent transfer reactions result in a strong preference for this cofactor compared, for example, to other methyl donors such as N5-methyltetrahydrofolate. Due to the electron lone pair in addition to the three different substituents, the sulfonium group is chiral, and the naturally occurring AdoMet (1) is S-configured at sulfur [5].Many other naturally occurring alkylated thioadenosines are derived from AdoMet (1) such as S-adenosyl-L-homocysteine (AdoHcy, also called SAH, 2) and 5 0 -deoxy-5 0 -methylthioadenosine (MTA, 3) (Scheme 9.3), although these compounds and their related 5 0 -thioethers are beyond the scope of this chapter. AdoMet (1) and its derivatives are involved in key metabolic reactions, cell cycle regulation and the storage of epigenetic information, which makes them not only highly interesting for studying biological pathways but also as in-vitro or in-vivo biochemical tools and candidates for diagnostics and therapeutics.

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Homochiral synthesis of an aza analogue of S-adenosyl-L-methionine (AdoMet) and its binding to the E. coli methionine repressor protein (MetJ)

Cited by 18 publications

References 19 publications

Isolation and structural elucidation of a growth stimulant for arbuscular mycorrhizal fungus from Laminaria japonica Areschoug

Isolation and structural elucidation of a growth stimulant for arbuscular mycorrhizal fungus from Laminaria japonica Areschoug

Encephalitozoon cuniculi mRNA Cap (Guanine N-7) Methyltransferase

S‐Adenosyl‐L‐Methionine and Related Compounds

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