5′-methylthioadenosine and related compounds as precursors of S-adenosylmethionine in yeast

Schlenk, F.; Zydek-Cwick, Cynthia R.; Dainko, J. L.

doi:10.1016/0304-4165(73)90316-4

Cited by 45 publications

(13 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the conversion of methionine to ethylene in apple tissue, the methylthio group is recycled through several steps to methionine (2 (18) found that 5'-methylthioadenosine was converted into methionine prior to its conversion to SAM in yeast. Recently, we have demonstrated that when 5'-methylthioadenosine-methyl-'4C was administered to apple tissue, the radioactivity was rapidly incorporated into methionine.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of in Vivo Conversion of Methionine to Ethylene by l-Canaline and 2,4-Dinitrophenol

Murr

Yang²

1975

Plant Physiol.

View full text Add to dashboard Cite

L-Canaline, a potent inhibitor of pyridoxal phosphate-mediated reactions, markedly inhibited the conversion of methionine to ethylene and carbon dioxide by apple tissue. A 50% inhibition of methionine conversion into ethylene was obtained with 50 jtM canaline and almost complete inhibition with 300 AM canaline. When 2, 4-dinitrophenol, an oxidative phosphorylation uncoupler, was fed to apple tissue, it inhibited the conversion of radioactive methionine to ethylene by 50% at a concentration of 60 AM and by 90% at a concentration of 100ItM. Production of labeled carbon dioxide from acetate-l-'4C was increased by 2,4-dinitrophenol, indicating that the inhibition of ethylene production was due to uncoupling of phosphorylation. Auxin-induced ethylene production by mungbean (Phaseolus mungo L.) hypocotyl sections was similarly inhibited by these inhibitors.These results support the proposal that pyridoxal phosphate is involved in the formation of ethylene from methionine, substantiate the requirement for ATP in ethylene production, and suggest that this ATP requirement occurs in the step(s) between methionine and ethylene. The biosynthetic mechanism probably involves activation of methionine by ATP followed by a pyridoxal phosphate-mediated y-elimination.Evidence from tracer studies has established methionine as the in vivo precursor of ethylene in fruit and vegetative tissues (1. 3,6,12,17,21). Conversion of methionine to ethylene in apple tissues represents the major pathway of methionine metabolism (6) and has an absolute requirement for 02 (3). A requirement for oxidative phosphorylation in the endogenous synthesis of ethylene has been demonstrated by inhibitor studies using respiratory uncouplers (8,11,20). Although DNP,2 a respiratory uncoupler, has been reported to inhibit the in vivo conversion of methionine to ethylene (4), the dependence of methionine conversion to ethylene on DNP concentration was not investigated.Recently it was found that rhizobitoxine, a phytotoxin produced by Rhizobium japonicum, markedly inhibited ethylene evolution by untreated and IAA-or kinetin-treated sorghum seedlings as well as inhibiting the formation of ethylene from 1 This work was supported by National Science Foundation Grant GB-33907X. (14) and spinach (10), Owens et al. (15) suggested that pyridoxal phosphate acted as a cofactor in the conversion of methionine to ethylene. Yang and Baur (21) proposed a concerted y-elimination reaction mechanism involving pyridoxal phosphate and 02 to account for the biological production of ethylene from methionine.We have found that L-canaline (2-amino-4-aminooxybutyric acid), a structural analog of L-ornithine, effectively inhibits the conversion of methionine to ethylene in apple tissue. L-Canaline has been shown to complex strongly with pyridoxal phosphate and inhibit activity of pyridoxal-dependent enzymes (16). This paper describes the effect of DNP and L-canaline on the conversion of L-methionine to ethylene in apple tissue and on the ethylene evolution by auxin-treated mu...

show abstract

Section: Discussionmentioning

confidence: 99%

Inhibition of in Vivo Conversion of Methionine to Ethylene by l-Canaline and 2,4-Dinitrophenol

Murr

Yang²

1975

Plant Physiol.

View full text Add to dashboard Cite

show abstract

“…The MTRK-ADP and the MTRK-AMPPCP complexes were prepared by overnight soaking of MTRK crystals in 25% (w/v) PEG2000MME, 0.3 M sodium acetate, 20 mM magnesium acetate, and either 4 mM ADP or AMP-PCP (sodium salt). The MTRK-AMPPCP-MTR complex was prepared by soaking the MTRK crystals in 25% (w/v) PEG2000MME, 0.3 M sodium acetate, 20 mM magnesium acetate, 4 mM AMPPCP, and 2 mM MTR for 2 h. The substrate MTR was synthesized by hydrolysis of MTA as described previously (22). We also attempted, by co-crystallization, to determine the structure of an MTRK-ATP complex.…”

Section: Methodsmentioning

confidence: 99%

Structures of 5-Methylthioribose Kinase Reveal Substrate Specificity and Unusual Mode of Nucleotide Binding

Yip

Cornell

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

The methionine salvage pathway is ubiquitous in all organisms, but metabolic variations exist between bacteria and mammals. 5-Methylthioribose (MTR) kinase is a key enzyme in methionine salvage in bacteria and the absence of a mammalian homolog suggests that it is a good target for the design of novel antibiotics. The structures of the apo-form of Bacillus subtilis MTR kinase, as well as its ADP, ADP-PO 4 , AMP-PCP, and AMPPCP-MTR complexes have been determined. MTR kinase has a bilobal eukaryotic protein kinase fold but exhibits a number of unique features. The protein lacks the DFG motif typically found at the beginning of the activation loop and instead coordinates magnesium via a DXE motif (Asp 250 -Glu 252 ). In addition, the glycine-rich loop of the protein, analogous to the "Gly triad" in protein kinases, does not interact extensively with the nucleotide. The MTR substratebinding site consists of Asp 233 of the catalytic HGD motif, a novel twin arginine motif (Arg 340 /Arg 341 ), and a semi-conserved W-loop, which appears to regulate MTR binding specificity. No lobe closure is observed for MTR kinase upon substrate binding. This is probably because the enzyme lacks the lobe closure/inducing interactions between the C-lobe of the protein and the ribosyl moiety of the nucleotide that are typically responsible for lobe closure in protein kinases. The current structures suggest that MTR kinase has a dissociative mechanism.Methionine is indispensable for cellular survival and is in high demand in proliferating cells. This essential amino acid plays critical roles in many ubiquitous cellular functions including protein synthesis, biological methylation, polyamine biosynthesis, as well as in the biosynthesis of the plant hormone ethylene and in some bacteria, quorum sensing. The biosynthesis of methionine is energetically costly, and the need for sufficient methionine has driven the evolution of methionine salvage pathways (1). Although the pathway is ubiquitous in almost all organisms, some metabolic variations are found in the pathways between mammals, plants, microbes, and certain parasitic protozoa. A key metabolic difference between mammals and prokaryotic pathogens is the absolute requirement for mtnK (2), which encodes 5-methylthioribose (MTR) 3 kinase (EC 2.7.1.100) (3) for bacterial methionine salvage.MTR kinase is regulated by the environmental methionine level (4) and its expression enables organisms to grow on nonmethionine sulfur sources such as MTR or 5Ј-methylthioadenosine (MTA) (5-7). MTA is a byproduct and inhibitor of polyamine synthesis (8) and hence is toxic to cells and must be rapidly degraded. In various microbes, plants, and certain protozoa, MTA is degraded by MTA nucleosidase into MTR and adenine. MTR kinase then catalyzes the phosphorylation of MTR to MTR 1-phosphate, which is subsequently converted to methionine via a series of intermediates (8, 9). In mammalian cells, however, the degradation of MTA and its conversion to MTR 1-phosphate is achieved in a single step by MTA phosphoryla...

show abstract

“…MTR was prepared by acid hydrolysis of MTA (18). Growth media containing MTA and MTR were filter sterilized.…”

Section: Methodsmentioning

confidence: 99%

In Vivo Metabolism of 5′-Methylthioadenosine in Lemna

Giovanelli¹,

Datko²,

Mudd³

et al. 1983

Plant Physiol.

View full text Add to dashboard Cite

show abstract

5′-methylthioadenosine and related compounds as precursors of S-adenosylmethionine in yeast

Cited by 45 publications

References 11 publications

Inhibition of in Vivo Conversion of Methionine to Ethylene by l-Canaline and 2,4-Dinitrophenol

Inhibition of in Vivo Conversion of Methionine to Ethylene by l-Canaline and 2,4-Dinitrophenol

Structures of 5-Methylthioribose Kinase Reveal Substrate Specificity and Unusual Mode of Nucleotide Binding

In Vivo Metabolism of 5′-Methylthioadenosine in Lemna

Contact Info

Product

Resources

About