%0 Journal Article
%T Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patients
%A Paola JS Provazzi
%A Helen A Arcuri
%A Isabel Maria VG de Carvalho-Mello
%A Jo£¿o Renato R Pinho
%A Maur¨ªcio L Nogueira
%A M¨¢rio S Palma
%A Paula Rahal
%J BMC Research Notes
%D 2010
%I BioMed Central
%R 10.1186/1756-0500-3-196
%X Evidence was found that the NS3 helicase portion of non-responder patients contained substitutions in its ATP and RNA binding sites. K210E substitution can cause an imbalance in the distribution of loads, leading to a decrease in the number of ligations between the essential amino acids required for the hydrolysis of ATP. W501R substitution causes an imbalance in the distribution of loads, leading and forcing the RNA to interact with the amino acid Thr269, but not preventing binding of ribavirin inhibitor.Useful information is provided on the genetic profiling of the HCV genotype 3, specifically the coding region of the NS3 protein, improving our understanding of the viral genome and the regions of its protein catalytic site.Hepatitis C virus (HCV) is the main causative agent of non-A and non-B hepatitis. The clinical manifestations of infection include acute and chronic forms of hepatitis C, liver cirrhosis and hepatocellular carcinoma [1]. The overall prevalence estimated of HCV infection is 2.2%, which corresponds to 130 million HCV-positive people in the world [2]. About 3 million people in Brazil are infected [3].The HCV genome contains a positive single-stranded RNA of ~9.6 kb. It encodes a single precursor polyprotein containing ~3000 amino acids [4-6], which gives rise to all viral structural proteins (S) - core (protein C), envelope 1 (E1) and envelope 2 (E2) - and nonstructural proteins (NS), located in the following order: NS2, NS3, NS4A, NS4B, NS5A, and NS5B [7].The NS3 protein of the hepatitis C virus (HCV) is a target for development of antiviral agents. It is a hydrophobic protein of ~69 kDa, with its serine-protease function encoded in its N-terminal portion accounting for one-third of the entire protein [7]. The C-terminal portion of the structural protein NS3 corresponds to the helicase domain, having NTPase and RNA helicase activities [8].To identify possible changes in the structure of the NS3 protein associated with virologically sustained respo
%U http://www.biomedcentral.com/1756-0500/3/196