 |
PDBsum entry 1ri2
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure and mechanism of mRNA cap (guanine-N7) methyltransferase.
|
|
|
Authors
|
|
C.Fabrega,
S.Hausmann,
V.Shen,
S.Shuman,
C.D.Lima.
|
|
|
Ref.
|
|
Mol Cell, 2004,
13,
77-89.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
A suite of crystal structures is reported for a cellular mRNA cap (guanine-N7)
methyltransferase in complex with AdoMet, AdoHcy, and the cap guanylate.
Superposition of ligand complexes suggests an in-line mechanism of methyl
transfer, albeit without direct contacts between the enzyme and either the N7
atom of guanine (the attacking nucleophile), the methyl carbon of AdoMet, or the
sulfur of AdoMet/AdoHcy (the leaving group). The structures indicate that
catalysis of cap N7 methylation is accomplished by optimizing proximity and
orientation of the substrates, assisted by a favorable electrostatic
environment. The enzyme-ligand structures, together with new mutational data,
fully account for the biochemical specificity of the cap guanine-N7 methylation
reaction, an essential and defining step of eukaryotic mRNA synthesis.
|
|
|
|
|
|
|
|
Figure 3.
Figure 3. Structures of the Active Site in Complex with
Ligands(A), (B), (C), and (E) are shown in stereo. Potential
hydrogen bonding interactions are shown by dashed lines, waters
as red spheres.(A) The Ecm1-AdoMet complex.(B) The Ecm1-AdoHcy
complex.(C) The Ecm1-cap complex.(D) 2.5 Å simulated
annealing map contoured at 1.0σ covering the cap guanylate
ligand.(E) The Ecm1-AdoHcy-cap complex.(F) 2.4 Å F[o] −
F[c] map contoured at 1.5σ covering the cap guanylate and
AdoHcy ligands.
|
|
Figure 5.
Figure 5. Electrostatic Surface DiagramsSurface
representations for the Ecm1-AdoHcy-cap complex in 180°
orientations. Electrostatic potential is shown on the Ecm1
surface and in contours at 2.0 k[b]T (blue) and −2.0 k[b]T
(red) to highlight the complementary electrostatics observed
for AdoMet (negative to counter the AdoMet positive charge)
and cap-binding sites (positive to counter the negative
phosphate charge). Electrostatic potential map and figure were
prepared using GRASP (Nicholls et al., 1991).
|
|
|
|
|
|
The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2004,
13,
77-89)
copyright 2004.
|
|
|
|
|
|
|
