The flavin coenzymes: a new class of group I intron inhibitors.
Effects of the coenzyme flavin mononucleotide (FMN) and its analogs on the self-splicing of primary transcripts of the phage T4 thymidylate synthase gene (td) have been investigated. Among all flavins and analogs tested, the lumichrome was the most inhibitory. The kinetic analysis demonstrated that FMN acts as a competitive inhibitor for the td intron RNA with a Ki of 1.86 mM although it does not possess a guanidino group in its structure. FMN is able to inhibit the first step of the self-splicing, thus identifying FMN as a novel class of group I intron splicing inhibitors. The specificity of the splicing inhibition by FMN is predominantly due to changes in Km but not k(cat). The splicing inhibition is believed to be due to the interference with the affinity of GTP for the intron RNA. The analysis of the inhibitory concentration and structural examination suggests that the key structural features in FMN responsible for the inhibition of splicing may be an alloxazine group.
Kim
J Y
JY
Department of Biology, Dongguk University, 100-715, Seoul, South Korea.
Park
I K
IK
D017122:Bacteriophage T4 / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005486:Flavin Mononucleotide / Q000031:analogs & derivatives / Q000494:pharmacology*; D005415:Flavins / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics; D007700:Kinetics; D011621:Pteridines / Q000494:pharmacology; D012326:RNA Splicing / Q000187:drug effects; D011994:Recombinant Proteins; D013940:Thymidylate Synthase / Q000235:genetics
D005415:Flavins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011621:Pteridines; D011994:Recombinant Proteins; C001559:7,8-dimethylalloxazine; C008297:lumazine; C008173:isoalloxazine; D005486:Flavin Mononucleotide; D006160:Guanosine Triphosphate; D013940:Thymidylate Synthase