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 (Comment) | Organism |
---|---|
expression of His-tagged alpha and beta subunits and of His-tagged mutant alpha-subunit | Homo sapiens |
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 | 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 | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | activates | Homo sapiens |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Homo sapiens | - |
- |
- |
Purification (Comment) | Organism |
---|---|
recombinant His-tagged alpha and beta subunits by affinity chromatography | Homo sapiens |
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 | Comment | Organism |
---|---|---|
ribonucleotide reductase | - |
Homo sapiens |
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 |