5'-O-dephosphorylated 2',5'-oligoadenylate (2-5A) with 8-methyladenosine at the 2'-terminus activates human RNase L.
Human ribonuclease L (RNase L), an interferon-induced endoribonuclease, becomes enzymatically active after binding to 2-5A. The 5'-phosphoryl group of 2-5A is reportedly necessary for the conformational change leading to RNase L activation. However, we found that 5'-O-dephosphorylated 2-5A tetramer analogs with 8-methyladenosine at the 2'-terminus were more effective as an activator of RNase L than the parent 2-5A tetramer. Introduction of 8-methyladenosine is thought to induce a dramatic shift of 2-5A in the binding site of RNase L.
Nagaoka
Kumi
K
United Graduate School of Drug Discovery and Medical Information Science, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Kitamura
Yoshiaki
Y
Ueno
Yoshihito
Y
Kitade
Yukio
Y
D000227:Adenine Nucleotides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D018360:Crystallography, X-Ray; D004722:Endoribonucleases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009843:Oligoribonucleotides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation; D011994:Recombinant Proteins / Q000378:metabolism; D012910:Snake Venoms
D000227:Adenine Nucleotides; D009843:Oligoribonucleotides; D011994:Recombinant Proteins; D012910:Snake Venoms; C070330:8-methyladenosine; C023505:2',5'-oligoadenylate; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D000241:Adenosine