1L9K

dengue methyltransferase

1L9K の概要

• エントリーDOI: 10.2210/pdb1l9k/pdb
• 分子名称: RNA-DIRECTED RNA POLYMERASE, SULFATE ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• 機能のキーワード: methyltransferase fold, complex with s-adenosyl-l-homocysteine, transferase
• 由来する生物種: Dengue virus
• 細胞内の位置: Capsid protein C: Virion (Potential). Peptide pr: Secreted (By similarity). Small envelope protein M: Virion membrane; Multi-pass membrane protein (By similarity). Envelope protein E: Virion membrane; Multi- pass membrane protein (By similarity). Non-structural protein 1: Secreted. Non-structural protein 2A-alpha: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Non-structural protein 2A: Host endoplasmic reticulum membrane; Multi-pass membrane protein (Potential). Serine protease subunit NS2B: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Serine protease NS3: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity). Non-structural protein 4A: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). Non-structural protein 4B: Host endoplasmic reticulum membrane; Multi-pass membrane protein (By similarity). RNA-directed RNA polymerase NS5: Host endoplasmic reticulum membrane; Peripheral membrane protein; Cytoplasmic side (By similarity): P12823
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35261.75

構造登録者

Egloff, M.P.,Benarroch, D.,Selisko, B.,Romette, J.L.,Canard, B. (登録日: 2002-03-25, 公開日: 2003-03-25, 最終更新日: 2024-02-14)

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 (2.4 Å)