1L9K

dengue methyltransferase

Summary for 1L9K

• Entry DOI: 10.2210/pdb1l9k/pdb
• Descriptor: RNA-DIRECTED RNA POLYMERASE, SULFATE ION, S-ADENOSYL-L-HOMOCYSTEINE, ... (4 entities in total)
• Functional Keywords: methyltransferase fold, complex with s-adenosyl-l-homocysteine, transferase
• Biological source: Dengue virus
• Cellular location: 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
• Total number of polymer chains: 1
• Total formula weight: 35261.75

Authors

Egloff, M.P.,Benarroch, D.,Selisko, B.,Romette, J.L.,Canard, B. (deposition date: 2002-03-25, release date: 2003-03-25, Last modification date: 2024-02-14)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.4 Å)