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Literature summary extracted from

  • Xu, H.; Fairman, J.W.; Wijerathna, S.R.; Kreischer, N.R.; LaMacchia, J.; Helmbrecht, E.; Cooperman, B.S.; Dealwis, C.
    The structural basis for peptidomimetic inhibition of eukaryotic ribonucleotide reductase: a conformationally flexible pharmacophore (2008), J. Med. Chem., 51, 4653-4659.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
1.17.4.1 medicine the enzyme is a target for cancer therapy Saccharomyces cerevisiae

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.17.4.1 expression of His-tagged subunits R2 and R4 in Escherichia coli strain BL21(DE3) Saccharomyces cerevisiae

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.17.4.1 purified enzyme, formed by recombinant subunits R2 and R4, complexed with inhibitor peptide P7 or peptide Fmoc-P6, 20 mg/ml protein in 0.1 M HEPES, pH 7.5, with 20 mM TTP, 5% glycerol, 5mM DTT, 0.1 M KCL, and 25 mm MgCl2, is mixed with a reservoir solution containing 20-25% PEG 3350, 0.2 M NaCl, and 100 mM HEPES, pH 7.5, soaking of crystals for 4 h in reservoir solution with added inhibitor peptide P6 or P7, followed by soaking of crystals in 25% PEG 3350, 0.2 M NaCl, and 100 mM HEPES, pH 7.5, supplemented with 15% glycerol, X-ray diffraction structure determination and analysis at 2.6 and 2.5 A resolution, respectively Saccharomyces cerevisiae

Protein Variants

EC Number Protein Variants Comment Organism
1.17.4.1 additional information construction of heterochimeric enzymes as heterocomplexes containing mammalian R2 C-terminal heptapeptide P7, Ac-1FTLDADF7, and its peptidomimetic P6, 1Fmoc(Me)PhgLDChaDF7, bound to Saccharomyces cerevisiae R1, ScR1, overview Saccharomyces cerevisiae

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.17.4.1 mammalian R2 C-terminal heptapeptide P7 Ac-1FTLDADF7, the inhibitor binds at bind at a contiguous site containing residues that are highly conserved among eukaryotes, binding structure, overview Saccharomyces cerevisiae
1.17.4.1 peptide P6 1Fmoc(Me)PhgLDChaDF7, the inhibitor binds at a contiguous site containing residues that are highly conserved among eukaryotes. The Fmoc group in P6 peptide forms several hydrophobic interactions that contribute to its enhanced potency in binding to ScR1, binding structure, overview Saccharomyces cerevisiae

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.17.4.1 GDP + thioredoxin Saccharomyces cerevisiae
-
 2'-deoxyGDP + thioredoxin disulfide + H2O
-
 ?
1.17.4.1 ribonucleoside diphosphate + thioredoxin Saccharomyces cerevisiae
-
 2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.17.4.1 Saccharomyces cerevisiae P21524
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.17.4.1 recombinant His-tagged subunits R2 and R4 from Escherichia coli strain BL21(DE3) by nickel affinity chromatography and dialysis Saccharomyces cerevisiae

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.17.4.1 GDP + thioredoxin
-
 Saccharomyces cerevisiae 2'-deoxyGDP + thioredoxin disulfide + H2O
-
 ?
1.17.4.1 ribonucleoside diphosphate + thioredoxin
-
 Saccharomyces cerevisiae 2'-deoxyribonucleoside diphosphate + thioredoxin disulfide + H2O
-
 ?

Subunits

EC Number Subunits Comment Organism
1.17.4.1 tetramer the enzyme activity requires formation of a complex between subunits R1 and R2 in which the R2 C-terminal peptide binds to R1 Saccharomyces cerevisiae

Synonyms

EC Number Synonyms Comment Organism
1.17.4.1 ribonucleotide reductase
-
 Saccharomyces cerevisiae

Cofactor

EC Number Cofactor Comment Organism Structure
1.17.4.1 thioredoxin
-
 Saccharomyces cerevisiae

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.17.4.1 0.0026
-
 yeast enzyme Saccharomyces cerevisiae peptide Fmoc-P6
1.17.4.1 0.031
-
 yeast enzyme Saccharomyces cerevisiae peptide P7