2p1d

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Revision as of 19:19, 29 January 2008

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spinqualitylabelsall models 2p1d, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Overview

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.

About this Structure

2P1D is a Single protein structure of sequence from Dengue virus type 3 with , and as ligands. Active as RNA-directed RNA polymerase, with EC number 2.7.7.48 Full crystallographic information is available from OCA.

Reference

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

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