NDLI: Structurally Conserved Amino Acid W501 Is Required for RNA Helicase Activity but Is Not Essential for DNA Helicase Activity of Hepatitis C Virus NS3 Protein

Content Provider	PubMed Central
Author	Kim, Jong Won Seo, Mi Young Shelat, Anang Kim, Chon Saeng Kwon, Tae Woo Lu, Hui-hua Moustakas, Demetri Theodore Sun, Jeonghoon Han, Jang H.
Copyright Year	2003
Abstract	Hepatitis C virus (HCV) is a positive-strand RNA virus that encodes a helicase required for viral replication. Although HCV does not replicate through a DNA intermediate, HCV helicase unwinds both RNA and DNA duplexes. An X-ray crystal structure of the HCV helicase complexed with (dU)8 has been solved, and the substrate-amino acids interactions within the catalytic pocket were shown. Among these, residues W501 and V432 were reported to have base stacking interactions and to be important for the unwinding function of HCV helicase. It has been hypothesized that specific interactions between the enzyme and substrate in the catalytic pocket are responsible for the substrate specificity phenotype. We therefore mutagenized W501 and V432 to investigate their role in substrate specificity in HCV helicase. Replacement of W501, but not V432, with nonaromatic residues resulted in complete loss of RNA unwinding activity, whereas DNA unwinding activity was largely unaffected. The loss of unwinding activity was fully restored in the W501F mutant, indicating that the aromatic ring is crucial for RNA helicase function. Analysis of ATPase and nucleic acid binding activities in the W501 mutant enzymes revealed that these activities are not directly responsible for the substrate specificity phenotype. Molecular modeling of the enzyme-substrate interaction at W501 revealed a putative π-facial hydrogen bond between the 2′-OH of ribose and the aromatic tryptophan ring. This evidence correlates with biochemical results suggesting that the π-facial bond may play an important role in the RNA unwinding activity of the HCV NS3 protein.
Related Links	http://dx.doi.org/10.1128/jvi.77.1.571-582.2003
Ending Page	582
Page Count	12
Starting Page	571
File Format	PDF
ISSN	0022538X
e-ISSN	10985514
Journal	Journal of Virology
Issue Number	1
Volume Number	77
Language	English
Publisher	American Society for Microbiology
Publisher Date	2003-01-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Immunology Virology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Virology Immunology Microbiology Insect Science

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