Specific inhibition of ribonucleotide reductases by peptides corresponding to the C-terminal of their second subunit.
Previous studies have shown that herpes virus ribonucleotide reductase can be inhibited by a synthetic nonapeptide whose sequence is identical to the C-terminal of the small subunit of the enzyme. This peptide is able to interfere with normal subunit association that takes place through the C-terminal of the small subunit. In this report, we illustrate that inhibition of ribonucleotide reductases by peptides corresponding to the C-terminal of subunit R2 is also observed for the enzyme isolated from Escherichia coli, hamster, and human cells. The nonapeptide corresponding to the bacterial C-terminal sequence was found to inhibit E. coli enzyme with an IC50 of 400 microM, while this peptide had no effect on mammalian ribonucleotide reductase. A corresponding synthetic peptide derived from the C-terminal of the small subunit of the human enzyme inhibited both human and hamster ribonucleotide reductases with IC50 values of 160 and 120 microM, respectively. However, this peptide had no inhibitory activity against the bacterial enzyme. Equivalent peptides derived from herpes virus ribonucleotide reductase had no effect on either the bacterial or mammalian enzymes. Thus, subunit association at the C-terminal of the small subunit appears to be a common feature of ribonucleotide reductases. In addition, the inhibitory phenomenon observed with peptides corresponding to the C-terminal appears not only to be universal, but also specific to the primary sequence of the enzyme.
Cosentino
G
G
Bio-Méga, Inc., Laval Québec, Canada.
Lavallée
P
P
Rakhit
S
S
Plante
R
R
Gaudette
Y
Y
Lawetz
C
C
Whitehead
P W
PW
Duceppe
J S
JS
Lépine-Frenette
C
C
Dansereau
N
N
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D001414:Bacitracin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D004926:Escherichia coli / Q000201:enzymology; D006564:Herpesviridae / Q000201:enzymology; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity
D010446:Peptide Fragments; D001414:Bacitracin; D012264:Ribonucleotide Reductases