2P1D

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

2P1D の概要

• エントリーDOI: 10.2210/pdb2p1d/pdb
• 関連するPDBエントリー: 1L9K
• 分子名称: type II methyltransferase, SULFATE ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (5 entities in total)
• 機能のキーワード: vizier; viral enzymes involved in replication; dengue virus methyltransferase; structural genomics; marseilles structural genomics program @ afmb; msgp, vizier. viral enzymes involved in replication, viral protein, transferase
• 由来する生物種: Dengue virus 2
• 細胞内の位置: Envelope protein E: Virion membrane; Multi- pass membrane protein: Q9WLZ8
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 36105.29

構造登録者

Egloff, M.P.,Benarooch, D.,Marseilles Structural Genomics Program @ AFMB (MSGP) (登録日: 2007-03-05, 公開日: 2007-03-20, 最終更新日: 2023-08-30)

主引用文献

Egloff, M.P.,Benarroch, D.,Selisko, B.,Romette, J.L.,Canard, B.
An RNA cap (nucleoside-2'-O)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization
EMBO J., 21:2757-2768, 2002

PubMed Abstract: 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.

PubMed: 12032088
DOI: 10.1093/emboj/21.11.2757

実験手法

X-RAY DIFFRACTION (2.9 Å)