Structure/function analysis of an RNA aptamer for hepatitis C virus NS3 protease.

Structure/function analysis of an RNA aptamer for hepatitis C virus NS3 protease. Research Abstract Details 

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Structure/function analysis of an RNA aptamer for hepatitis C virus NS3 protease. Abstract Text:

Satoru Sekiya,Fumiko Nishikawa,Kotaro Fukuda,Satoshi Nishikawa,

RNA aptamers that bind specifically to hepatitis C virus (HCV) NS3 protease domain (DeltaNS3) were identified in previous studies. These aptamers, G9-I, -II, and -III, were isolated using an in vitro selection method and they share a common loop with the sequence 5'-GA(A/U)UGGGAC-3'. The aptamers are potent inhibitors of the NS3 protease in vitro and may have potential as anti-HCV compounds. G9-I has a 3-way stem-loop structure and was selected for further characterization using site-directed mutagenesis. Mutations or deletions in stem-loop II do not interfere with binding or inhibition of DeltaNS3, but mutations or deletions in stem I and stem-loop III destroy the G9-I active conformation and interfere with inhibition of NS3 protease. A 51 nt fragment of 74 nt G9-I was identified (DeltaNEO-III) as is the minimal fragment of G9-I that is an effective inhibitor of the NS3 protease. Tertiary interactions involving functionally important nucleotides were identified in the active structure of G9-I using nucleotide analog interference mapping (NAIM). Strong interferences were focused in the conserved loop involving stem-loop III and stem I. For example, analog-interference caused at A(+8) and C(+24)-G(-36) base pair implied an A-minor motif involving the intramolecular base triple A(+8).C(+24)-G(-36), which is further supported by mutagenesis. These results suggested the interaction of stem I and stem-loop III is essential for the function of G9-I aptamer.

Structure/function analysis of an RNA aptamer for hepatitis C virus NS3 protease. Publishing Authors By Initials

S Sekiya,F Nishikawa,K Fukuda,S Nishikawa,

For similar proteins: viral proteins: viral nonstructural proteins research abstracts see: proteins: viral proteins: viral nonstructural proteins research

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Structure/function analysis of an RNA aptamer for hepatitis C virus NS3 protease. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of biochemistry

VOLUME: 133

Page Numbers: 351-9

Journal Abbreviation: J. Biochem.

ISSN: 0021-924X

DAY: 19

MONTH: Mar

YEAR: 2003

Structure/function analysis of an RNA aptamer for hepatitis C virus NS3 protease. Information

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LANGUAGE: eng

NlmUniqueID: 376600

Structure/function analysis of an RNA aptamer for hepatitis C virus NS3 protease. Keywords Mesh Terms:

KEYWORDS: Viral Nonstructural Proteins

MESH TERMS: physiology

Chemical & Substance for Abstract: Structure/function analysis of an RNA aptamer for hepatitis C virus NS3 protease. Information

Substance Name: Viral Nonstructural Proteins

Registry Number: 0

Grant and Affiliation Information for Structure/function analysis of an RNA aptamer for hepatitis C virus NS3 protease.

AFFILIATION: Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.

Country: Japan

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MEDLINETA: J Biochem

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