TAILIEUCHUNG - Báo cáo khoa học: Contribution of Tyr712 and Phe716 to the activity of human RNase

Ribonuclease L (RNase L) is a key enzyme in the 2-5A host defense system, and its activity is strictly regulated by an unusual 2¢,5¢-linked oligoadenylate (2-5A).A bipartite model, in which the N-terminal half of RNase L is responsible for the 2-5A binding and the C-terminal half alone is able to hydrolyse the substrate RNA, has been proposed on the basis of the results of deletion mutant analyses [Dong, B.& Silverman, . | Eur. J. Biochem. 271 2737-2744 2004 FEBS 2004 doi Contribution of Tyr712 and Phe716 to the activity of human RNase L Masayuki Nakanishi Akihiro Yoshimura Norihisa Ishida Yoshihito Ueno and Yukio Kitade Laboratory of Molecular Biochemistry Department of Biomolecular Science Faculty of Engineering Gifu University Japan Ribonuclease L RNase L is a key enzyme in the 2-5A host defense system and its activity is strictly regulated by an unusual 2 5 -linked oligoadenylate 2-5A . A bipartite model in which the N-terminal half of RNase L is responsible for the 2-5A binding and the C-terminal half alone is able to hydrolyse the substrate RNA has been proposed on the basis of the results of deletion mutant analyses Dong B. Silvennan . 1997 J. Biol. Chem. 272 22236-22242 . Abwe ah tee region between Glu711 and Ris720 was revealed to be essential for RNA binding and or hydrolysis. To disecct the function of the region we performed scanning mutagenesis over the 10 residues of glutathione S-transferase GST -fusion RNase L. Aion ng rite nigele ammo add mutants examined Y712A and F716A resulted in a significant decrease of RNase activity with a reduced RNA binding losses of the RNase activity were not restored by its conservative mutation whereas the RNA binding activity was enhanced in the case of results indicate that both Tyr712 and Phe716 provide the enzyme with a RNA binding activity and catalytic environment. Keywords interferon RNase L scanning mutagenesis 2-5A system. Ribonuclease L RNase L 2 5 -oligoadenylate 2-5A and 2-5A synthetases are components of the 2-5A system 1 which is involved in a variety of host defence functions including antivirus infection 2 apoptosis 3 modulation of interferon action 4 and suppression of prostate cancer 5 . ylJl te functions are attiihutal to the breakdown of RNA by RNase L which hampers protein synthesis. The toxic activity of RNase L is strictly regulated so as not to occur in

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