Differences in the properties of mammalian ribonucleotide reductase toward its substrates.
These studies, using three different reagents, show that the substrate properties of ribonucleotide reductase are specific but can be variable depending upon the nature of the interaction of the reagent with the holoenzyme or the individual subunit. Etheno-CDP, which acts as a competitive inhibitor with respect to CDP, interacts with the active site of the holoenzyme. This interaction was the result of rather tight structural requirements as epsilon-ADP did not result in a similar level of inhibition of either CDP or ADP reductase activities. The YL 1/2 antibody which binds very tightly to the NHI subunit has a much greater effect on CDP reductase activity than ADP reductase activity. The nonapeptide that corresponds to the C-terminus amino acid sequence of the NHI subunit and which binds to the EB subunit and aborts the formation of the NHI-EB active complex has a greater effect on ADP reductase activity than on CDP reductase activity. The use of reagents such as these can be helpful in dissecting the subtle but important differences in the substrate properties of mammalian ribonucleotide reductase.
Cory
J G
JG
Department of Biochemistry, East Carolina University, School of Medicine, Greenville, NC 27858, USA.
Downes
D L
DL
Cory
A H
AH
D000266:Adenylyl Imidodiphosphate / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001665:Binding Sites; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019159:Nonheme Iron Proteins / Q000737:chemistry / Q000378:metabolism; D009711:Nucleotides / Q000378:metabolism* / Q000494:pharmacology*; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D012264:Ribonucleotide Reductases / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D013379:Substrate Specificity; D014404:Tubulin / Q000276:immunology; D015003:Yeasts / Q000737:chemistry
D000911:Antibodies, Monoclonal; D004791:Enzyme Inhibitors; D019159:Nonheme Iron Proteins; D009711:Nucleotides; D010446:Peptide Fragments; D014404:Tubulin; D000266:Adenylyl Imidodiphosphate; D012264:Ribonucleotide Reductases