2P1D

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


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.246 
  • R-Value Observed: 0.211 

Starting Model: experimental
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This is version 1.3 of the entry. See complete history


Literature

An RNA cap (nucleoside-2'-O)-methyltransferase in the flavivirus RNA polymerase NS5: crystal structure and functional characterization

Egloff, M.P.Benarroch, D.Selisko, B.Romette, J.L.Canard, B.

(2002) EMBO J 21: 2757-2768

  • DOI: https://doi.org/10.1093/emboj/21.11.2757
  • Primary Citation of Related Structures:  
    1L9K, 2P1D

  • 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.


  • Organizational Affiliation

    Architecture et Fonction des Macromolécules Biologiques, UMR 6098 CNRS et Université Aix-Marseille I et II, ESIL, Campus de Luminy, F-13288 Marseille Cedex 09, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
type II methyltransferase305dengue virus type 2Mutation(s): 0 
Gene Names: NSP5
EC: 2.7.7.48
UniProt
Find proteins for P12823 (Dengue virus type 2 (strain Puerto Rico/PR159-S1/1969))
Explore P12823 
Go to UniProtKB:  P12823
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP12823
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SAH
Query on SAH

Download Ideal Coordinates CCD File 
L [auth A]S-ADENOSYL-L-HOMOCYSTEINE
C14 H20 N6 O5 S
ZJUKTBDSGOFHSH-WFMPWKQPSA-N
5GP
Query on 5GP

Download Ideal Coordinates CCD File 
M [auth A]GUANOSINE-5'-MONOPHOSPHATE
C10 H14 N5 O8 P
RQFCJASXJCIDSX-UUOKFMHZSA-N
SO4
Query on SO4

Download Ideal Coordinates CCD File 
B [auth A]
C [auth A]
D [auth A]
E [auth A]
F [auth A]
B [auth A],
C [auth A],
D [auth A],
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A]
SULFATE ION
O4 S
QAOWNCQODCNURD-UHFFFAOYSA-L
Binding Affinity Annotations 
IDSourceBinding Affinity
SAH BindingDB:  2P1D IC50: 490 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.246 
  • R-Value Observed: 0.211 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 112.198α = 90
b = 112.198β = 90
c = 56.462γ = 120
Software Package:
Software NamePurpose
ADSCdata collection
AMoREphasing
CNSrefinement
MOSFLMdata reduction
CCP4data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-03-20
    Type: Initial release
  • Version 1.1: 2008-04-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description