||The NS5 proteins of all flaviviruses consist of at least three very important enzymatic functions which are essential for viral propagation (Khromykh et al., 1998, Hanley et al., 2002). Located at NS5’s N-terminus is the S-adenosyl-L-methionine dependent methyltransferase (SAM) domain (amino acids 1-320) which possess the methyl transferase and guanylyl transferase activity responsible for capping and methylating the capped the positive strand genomic RNA on its 5’ terminus (Egloff et al., 2002). The C-terminal domain encodes the RNA dependent RNA polymerase (residues 420-900) responsible for synthesizing the double stranded replicative intermediate RNA template and also plus strand RNA genomic RNA (Bartholomeusz & Thompson 1999, Egloff et al., 2002, Nomaguchi et al., 2003). The RdRp activity of this domain has been demonstrated for several other flaviviruses including West Nile virus, Kunjin virus, Hepatitis C viruses (HCV) and BVDV (Guyatt et al., 2001, Steffens et al., 1999, Tan et al., 1996, Khromykh et al., 1998). Two of these RdRps, namely the HCV and BVDV has been crystallized (Bressanelli et al., 2001, Choi et al., 2004). In all Flavivirus RNA dependent RNA polymerase, there is an essential GDD motif in which mutations on this motif renders the virus non-replicative (Khromykh et al., 1998, Ranjith-Kumar et al., 2001).
||None of the Dengue polymerase had been published. However, the structure of the two distantly related flaviviral polymerases, the BVDV and HCV had been reported (Bressanelli et al., 2001, Choi et al., 2004). In addition, the structure of methyl transferase domain of Dengue 2 strain NGC had been reported (Dutartre et al., 2005, Egloff et al., 2002).
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