 |
PDBsum entry 2ac5
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Crystal structures of the mnk2 kinase domain reveal an inhibitory conformation and a zinc binding site.
|
|
|
Authors
|
|
R.Jauch,
S.Jäkel,
C.Netter,
K.Schreiter,
B.Aicher,
H.Jäckle,
M.C.Wahl.
|
|
|
Ref.
|
|
Structure, 2005,
13,
1559-1568.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
Human mitogen-activated protein kinases (MAPK)-interacting kinases 1 and 2 (Mnk1
and Mnk2) target the translational machinery by phosphorylation of the
eukaryotic initiation factor 4E (eIF4E). Here, we present the 2.1 A crystal
structure of a nonphosphorylated Mnk2 fragment that encompasses the kinase
domain. The results show Mnk-specific features such as a zinc binding motif and
an atypical open conformation of the activation segment. In addition, the ATP
binding pocket contains an Asp-Phe-Asp (DFD) in place of the canonical magnesium
binding Asp-Phe-Gly (DFG) motif. The phenylalanine of this motif sticks into the
ATP binding pocket and blocks ATP binding as observed with inhibitor bound and,
thus, inactive p38 kinase. Replacement of the DFD by the canonical DFG motif
affects the conformation of Mnk2, but not ATP binding and kinase activity. The
results suggest that the ATP binding pocket and the activation segment of Mnk2
require conformational switches to provide kinase activity.
|
|
|
|
|
|
|
