5-Methylthioribose kinase. A new enzyme involved in the formation of methionine from 5-methylthioribose.

Ferro, Adolph J.; Barrett, Annabella; Shapiro, Stuart

doi:10.1016/s0021-9258(17)34573-8

Cited by 61 publications

(3 citation statements)

References 21 publications

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“…However, it should be noted that the elution profile of activity from the S200HR column is quite broad, thus we cannot accurately assess the subunit make-up of the native enzyme. The substrate affinity displayed by the purified kinase (K m for MTR of 12.2 µM) is similar to the Michaelis constants determined by other investigators for partially purified enzymes [4,28,33].…”

Section: Discussionsupporting

confidence: 85%

Affinity purification of 5-methylthioribose kinase and 5-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Klebsiella pneumoniae

Cornell

Winter²,

Tower

et al. 1996

Biochemical Journal

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Two enzymes in the methionine salvage pathway, 5-methylthioribose kinase (MTR kinase) and 5'-methylthioadenosine/ S-adenosylhomocysteine nucleosidase (MTA/SAH nucleosidase) were purified from Klebsiella pneumoniae. Chromatography using a novel 5'-(p-aminophenyl)thioadenosine/5-(p-aminophenyl)thioribose affinity matrix allowed the binding and selective elution of each of the enzymes in pure form. The molecular mass, substrate kinetics and N-terminal amino acid sequences were characterized for each of the enzymes. Purified MTR kinase exhibits an apparent molecular mass of 46-50 kDa by SDS/PAGE and S200HR chromatography, and has a Km for MTR of 12.2 microM. Homogeneous MTA/SAH nucleosidase displays a molecular mass of 26.5 kDa by SDS/PAGE, and a Km for MTA of 8.7 microM. Comparisons of the N-terminal sequences obtained for each of the enzymes with protein-sequence databases failed to reveal any significant sequence similarities to known proteins. However, the amino acid sequence obtained for the nucleosidase did share a high degree of sequence similarity with the putative translation product of an open reading frame in Escherichia coli, thus providing a tentative identification of this gene as encoding an MTA/SAH nucleosidase.

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Section: Discussionsupporting

confidence: 85%

Affinity purification of 5-methylthioribose kinase and 5-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Klebsiella pneumoniae

Cornell

Winter²,

Tower

et al. 1996

Biochemical Journal

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“…This pathway has been well characterized in Klebsiella pneumoniae, beginning with nucleosidase cleavage of MTA to adenine and 5-methylthioribose (63). The C-1 hydroxyl group of the ribose moiety of methylthioribose is in turn phosphorylated by methylthioribose kinase, producing methylthioribose 1-phosphate (69). After isomerization and dehydration to the diketo intermediate, the molecule is oxidatively decarboxylated to 2-keto-4-methylthiobutyrate, the immediate precursor of methionine (5).…”

Section: Methylthioadenosine Cyclementioning

confidence: 99%

Metabolism of sulfur amino acids in Saccharomyces cerevisiae.

Thomas¹,

Surdin-Kerjan²

1997

Microbiology and Molecular Biology Reviews : MMBR

519

333

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“…We recognized that direct 1-phosphorylation of 5-S-methylthioribose (MTR) occurs as part of the methionine salvage pathway and is catalyzed by MTR kinases (Figure S4). , Although MTR kinases do not naturally participate in nucleoside biosynthesis and have no reported biocatalytic applications, we hypothesized that an MTR kinase could generate the desired ribosyl-1-phosphate intermediate. A panel of MTR kinase enzymes was produced by heterologous expression in E. coli .…”

Section: Resultsmentioning

confidence: 99%

Engineered Ribosyl-1-Kinase Enables Concise Synthesis of Molnupiravir, an Antiviral for COVID-19

et al. 2021

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Molnupiravir (MK-4482) is an investigational antiviral agent that is under development for the treatment of COVID-19. Given the potential high demand and urgency for this compound, it was critical to develop a short and sustainable synthesis from simple raw materials that would minimize the time needed to manufacture and supply molnupiravir. The route reported here is enabled through the invention of a novel biocatalytic cascade featuring an engineered ribosyl-1-kinase and uridine phosphorylase. These engineered enzymes were deployed with a pyruvate-oxidase-enabled phosphate recycling strategy. Compared to the initial route, this synthesis of molnupiravir is 70% shorter and approximately 7-fold higher yielding. Looking forward, the biocatalytic approach to molnupiravir outlined here is anticipated to have broad applications for streamlining the synthesis of nucleosides in general.

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5-Methylthioribose kinase. A new enzyme involved in the formation of methionine from 5-methylthioribose.

Cited by 61 publications

References 21 publications

Affinity purification of 5-methylthioribose kinase and 5-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Klebsiella pneumoniae

Affinity purification of 5-methylthioribose kinase and 5-methylthioadenosine/S-adenosylhomocysteine nucleosidase from Klebsiella pneumoniae

Metabolism of sulfur amino acids in Saccharomyces cerevisiae.

Engineered Ribosyl-1-Kinase Enables Concise Synthesis of Molnupiravir, an Antiviral for COVID-19

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