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Literature summary for 1.17.4.1 extracted from

  • Aye, Y.; Stubbe, J.
    Clofarabine 5-di and -triphosphates inhibit human ribonucleotide reductase by altering the quaternary structure of its large subunit (2011), Proc. Natl. Acad. Sci. USA, 108, 9815-9820.
    View publication on PubMedView publication on EuropePMC

Activating Compound

Activating Compound Comment Organism Structure
ATP stimulates the reduction of CDP and ADP Homo sapiens
dGTP stimulates the reduction of CDP and ADP Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
expression of His-tagged alpha and beta subunits and of His-tagged mutant alpha-subunit Homo sapiens

Protein Variants

Protein Variants Comment Organism
D57N site-directed mutagenesis, binding kinetics to clofarabine di- and triphosphate inhibitors compared to the wild-type enzyme, overview Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
clofarabine an adenosine analogue is used in the treatment of refractory leukemias. Its mode of cytotoxicity is associated in part with the triphosphate functioning as an allosteric reversible inhibitor of hRNR, rapid inactivation Homo sapiens
clofarabine diphosphate ClFDP, a C-site slow-binding, reversible inhibitor, mechanism of inhibition via altering the quaternary structure of the large subunit of RNR, overview. Binds also mutant D57N-alpha subunit. CDP protects against inhibition Homo sapiens
clofarabine triphosphate ClFTP, an A-site rapidly binding reversible inhibitor, mechanism of inhibition via altering the quaternary structure of the large subunit of RNR, overview. Neither CDP (C site) nor dGTP (A site) had any effect on inhibition by ClFTP Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ activates Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Purification (Commentary)

Purification (Comment) Organism
recombinant His-tagged alpha and beta subunits by affinity chromatography Homo sapiens

Subunits

Subunits Comment Organism
oligomer RNRs are composed of alpha- and beta-subunits that form active (alpha)n(beta)m, with n or m being 2 or 6, complexes. Subunit alpha binds NDP substrates, i.e. CDP, UDP, ADP, and GDP, C site, as well as ATP and dNTPs, i.e. dATP, dGTP, TTP, allosteric effectors that control enzyme activity (A site) and substrate specificity, S site Homo sapiens

Synonyms

Synonyms Comment Organism
ribonucleotide reductase
-
Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
additional information
-
additional information inhibition kinetics of clofarabine di- and triphosphates, overview Homo sapiens
0.00004
-
clofarabine pH not specified in the publication, temperature not specified in the publication Homo sapiens