title: Mechanism of inhibition of herpes simplex virus (HSV) ribonucleotide reductase by a nonapeptide corresponding to the carboxyl terminus of its subunit 2. Specific binding of a photoaffinity analog, [4'- azido-Phe6] HSV H2-6(6-15), to subunit 1.
abstract: Herpes simplex virus (HSV) ribonucleotide reductase activity is specifically inhibited by a synthetic peptide, Tyr-Ala-Gly-Ala-Val-Val-Asn-Asp-Leu (HSV H2-(7-15], corresponding to the carboxyl terminus of its subunit 2 (H2). In order to elucidate the mechanism of action of the nonapeptide a photoreactive analog, [4'-azido-Phe6]HSV H2-(6-15), was synthesized. The photoaffinity probe inhibits HSV ribonucleotide reductase activity, and when radioiodinated, it specifically labeled three viral proteins of 144, 95, and 85 kDa. We demonstrated by immunoprecipitation of the 144- and 95-kDa photolabeled proteins with antibodies specific to subunit 1 (H1) of HSV ribonucleotide reductase that the nonapeptide interacts with H1 and probably with its degradation products. Moreover, we obtained evidence that this specific binding is directly responsible for the ribonucleotide reductase inhibition.
authors.affiliation: Institut du Cancer de Montréal, Notre-Dame Hospital, Quebec, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Paradis
authors.forename: P
authors.initials: P
authors.lastname: Gaudreau
authors.forename: P
authors.initials: P
authors.lastname: Brazeau
authors.forename: Y
authors.initials: Y
authors.lastname: Langelier
mesh_terms: D000345:Affinity Labels / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001386:Azides / Q000138:chemical synthesis / Q000494:pharmacology*; D002460:Cell Line; D046911:Macromolecular Substances; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011485:Protein Binding; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D018139:Simplexvirus / Q000201:enzymology*
chemical_list: D000345:Affinity Labels; D001386:Azides; D046911:Macromolecular Substances; D009842:Oligopeptides; C057534:herpes simplex virus H2 (6-15), 4'-azido-Phe(6)-; D012264:Ribonucleotide Reductases