2p1d

Crystal structure of dengue methyltransferase in complex with GTP and S-Adenosyl-L-homocysteine

spinqualitylabelsall models 2p1d, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2p1d is a 1 chain structure with sequence from Dengue virus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: 5GP, SAH, SO4 Related: 1l9k Gene: NSP5 (Dengue virus 2) Activity: RNA-directed RNA polymerase, with EC number 2.7.7.48 Resources: FirstGlance, OCA, RCSB, PDBsum Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Viruses represent an attractive system with which to study the molecular basis of mRNA capping and its relation to the RNA transcription machinery. The RNA-dependent RNA polymerase NS5 of flaviviruses presents a characteristic motif of S-adenosyl-L-methionine-dependent methyltransferases at its N-terminus, and polymerase motifs at its C-terminus. The crystal structure of an N-terminal fragment of Dengue virus type 2 NS5 is reported at 2.4 A resolution. We show that this NS5 domain includes a typical methyltransferase core and exhibits a (nucleoside-2'-O-)-methyltransferase activity on capped RNA. The structure of a ternary complex comprising S-adenosyl-L-homocysteine and a guanosine triphosphate (GTP) analogue shows that 54 amino acids N-terminal to the core provide a novel GTP-binding site that selects guanine using a previously unreported mechanism. Binding studies using GTP- and RNA cap-analogues, as well as the spatial arrangement of the methyltransferase active site relative to the GTP-binding site, suggest that the latter is a specific cap-binding site. As RNA capping is an essential viral function, these results provide a structural basis for the rational design of drugs against the emerging flaviviruses. An RNA cap (nucleoside-2'-O-)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization.,Egloff MP, Benarroch D, Selisko B, Romette JL, Canard B EMBO J. 2002 Jun 3;21(11):2757-68. PMID:12032088 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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