Document Detail


NTPase and 5' to 3' RNA duplex-unwinding activities of the hepatitis E virus helicase domain.
MedLine Citation:
PMID:  20071563     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepatitis E virus (HEV) is a causative agent of acute hepatitis, and it is the sole member of the genus Hepevirus in the family Hepeviridae. The open reading frame 1 (ORF1) protein of HEV encodes nonstructural polyprotein with putative domains for methyltransferase, cysteine protease, helicase and RNA-dependent RNA polymerase. It is not yet known whether ORF1 functions as a single protein with multiple domains or is processed to form separate functional units. On the basis of amino acid conserved motifs, HEV helicase has been grouped into helicase superfamily 1 (SF-1). In order to examine the RNA helicase activity of the NTPase/helicase domain of HEV, the region (amino acids 960 to 1204) was cloned and expressed as histidine-tagged protein in Escherichia coli (HEV Hel) and purified. HEV Hel exhibited NTPase and RNA unwinding activities. Enzyme hydrolyzed all rNTPs efficiently, dATP and dCTP with moderate efficiency, while it showed less hydrolysis of dGTP and dTTP. Enzyme showed unwinding of only RNA duplexes with 5' overhangs showing 5'-to-3' polarity. We also expressed and purified two HEV Hel mutants. Helicase mutant I, with substitution in the nucleotide-binding motif I (GKS to GAS), showed 30% ATPase activity. Helicase mutant II, with substitutions in the Mg(2+) binding motif II (DEAP to AAAP), showed 50% ATPase activity. Both mutants completely lost ability to unwind RNA duplexes with 5' overhangs. These findings represent the first report demonstrating NTPase/RNA helicase activity of the helicase domain of HEV ORF1.
Authors:
Yogesh A Karpe; Kavita S Lole
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Publication Detail:
Type:  Journal Article     Date:  2010-01-13
Journal Detail:
Title:  Journal of virology     Volume:  84     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-09     Completed Date:  2010-03-30     Revised Date:  2010-10-04    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3595-602     Citation Subset:  IM    
Affiliation:
Hepatitis Division, National Institute of Virology, Microbial Containment Complex, Sus Road, Pashan, Pune, India 411021, USA.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphatases / metabolism
Hepatitis E virus / enzymology*
Nucleoside-Triphosphatase / chemistry,  isolation & purification,  metabolism*
Protein Structure, Tertiary
RNA Helicases / chemistry,  isolation & purification,  metabolism*
RNA, Viral / chemistry*
Chemical
Reg. No./Substance:
0/RNA, Viral; EC 2.7.7.-/RNA Helicases; EC 3.6.1.-/Adenosine Triphosphatases; EC 3.6.1.15/Nucleoside-Triphosphatase

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