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Titolo:
A phosphoramidate substrate analog is a competitive inhibitor of the Tetrahymena group I ribozyme
Autore:
Hanna, RL; Gryaznov, SM; Doudna, JA;
Indirizzi:
Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 ophys & Biochem, New Haven, CT 06520 USA Yale Univ, Howard Hughes Med Inst, New Haven, CT 06520 USA Yale Univ New Haven CT USA 06520 Hughes Med Inst, New Haven, CT 06520 USA Geron Corp, Menlo Park, CA 94025 USA Geron Corp Menlo Park CA USA 94025Geron Corp, Menlo Park, CA 94025 USA
Titolo Testata:
CHEMISTRY & BIOLOGY
fascicolo: 11, volume: 7, anno: 2000,
pagine: 845 - 854
SICI:
1074-5521(200011)7:11<845:APSAIA>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
TERTIARY INTERACTIONS; CRYSTAL-STRUCTURE; ACTIVE-SITE; ANTISENSE OLIGONUCLEOTIDES; INTERVENING SEQUENCE; PNEUMOCYSTIS-CARINII; CATALYTIC CORE; RNA MIMETICS; 2'-OH GROUPS; METAL-ION;
Keywords:
group I intron; inhibitor; phosphoramidate; ribozyme; substrate analog;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
50
Recensione:
Indirizzi per estratti:
Indirizzo: Doudna, JA Yale Univ, Dept Mol Biophys & Biochem, POB 6666, New Haven, CT 06520 USA Yale Univ POB 6666 New Haven CT USA 06520 w Haven, CT 06520 USA
Citazione:
R.L. Hanna et al., "A phosphoramidate substrate analog is a competitive inhibitor of the Tetrahymena group I ribozyme", CHEM BIOL, 7(11), 2000, pp. 845-854

Abstract

Background: Phosphoramidate oligonucleotide analogs containing N3'-P5' linkages share many structural properties with natural nucleic acids and can be recognized by some RNA-binding proteins. Therefore, if the N-P bond is resistant to nucleolytic cleavage, these analogs may be effective substrate analog inhibitors of certain enzymes that hydrolyze RNA. We have explored the ability of the Tetrahymena group I intron ribozyme to bind and cleave DNAand RNA phosphoramidate analogs. Results: The Tetrahymena group I ribozyme efficiently binds to phosphoramidate oligonucleotides but is unable to cleave the N3'-P5' bond. Although itadopts an A-form helical structure, the deoxyribo-phosphoramidate analog, like DNA, does not dock efficiently into the ribozyme catalytic core. In contrast, the ribophosphoramidate analog docks similarly to the native RNA substrate, and behaves as a competitive inhibitor of the group I intron 5' splicing reaction. Conclusions: Ribo-N3'-P5' phosphoramidate oligonucleotides are useful tools for structural and functional studies of ribozymes as well as protein-RNAinteractions.

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Documento generato il 04/04/20 alle ore 08:33:22