Fig. 1. General features of NS5MTaseDV. (A) Predicted domain structure of Dengue protein NS5. The putative N-terminal methyltransferase domain is shown in grey. The position of the AdoMet-binding motif I (residues 77–86) described by Koonin (1993) is highlighted in black. The region of the C-terminal polymerase domain containing motifs I to VIII of positive-strand RNA virus RNA polymerases (Koonin, 1991) is marked in grey. Motifs A to D, shared by RNA-dependent polymerases (Poch et al., 1989), are shown in black. AdoMet, S-adenosyl-l-methionine; NLS, nuclear localization sequence; Pol, polymerase. (B) Crystal structure of NS5MTaseDV in complex with AdoHcy. A ball-and-stick representation is used for AdoHcy, whereas NS5MTaseDV is drawn as a ribbon. The N-terminal subdomain of NS5MTaseDV (residues 7–54) is coloured red. The core subdomain (residues 55–222) has a typical AdoMet-dependent MTase topology and is coloured yellow. The C-terminal part of NS5MTaseDV (residues 223–267) is coloured cyan. The figure was generated using MOLSCRIPT (Kraulis, 1991) and rendered using RASTER3D (Merrit and Murphy, 1994). (C) Sequence alignment of flavivirus NS5MTases coloured according to the ribbon representation of NS5MTaseDV in (B). NS5MTase domains from Dengue virus type 2 New Guinea isolate (D2V), West Nile virus New York isolate (WNV) and Yellow Fever 17D (YFV) were aligned using Clustal_W (Thompson et al., 1994) and rendered using ESPript (Gouet et al., 1999). Secondary structures (α-helices and β-strands) of subdomains 1, 2 and 3 are indicated above the alignment and coloured in red, yellow and cyan, respectively. Helices and strands are named using Greek letters inside the core domain (subdomain 2), and roman letters outside (subdomains 1 and 3). Amino acids involved in GTP binding (see text) are indicated by a grey star below aligned sequences, and amino acids interacting with AdoHcy are indicated by a pink sphere.