 |
PDBsum entry 4jdk
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Transferase/peptide
|
PDB id
|
|
|
|
4jdk
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Identification of a major determinant for serine-Threonine kinase phosphoacceptor specificity.
|
|
|
Authors
|
|
C.Chen,
B.H.Ha,
A.F.Thévenin,
H.J.Lou,
R.Zhang,
K.Y.Yip,
J.R.Peterson,
M.Gerstein,
P.M.Kim,
P.Filippakopoulos,
S.Knapp,
T.J.Boggon,
B.E.Turk.
|
|
|
Ref.
|
|
Mol Cell, 2014,
53,
140-147.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Eukaryotic protein kinases are generally classified as being either tyrosine or
serine-threonine specific. Though not evident from inspection of their primary
sequences, many serine-threonine kinases display a significant preference for
serine or threonine as the phosphoacceptor residue. Here we show that a residue
located in the kinase activation segment, which we term the "DFG+1"
residue, acts as a major determinant for serine-threonine phosphorylation site
specificity. Mutation of this residue was sufficient to switch the
phosphorylation site preference for multiple kinases, including the
serine-specific kinase PAK4 and the threonine-specific kinase MST4. Kinetic
analysis of peptide substrate phosphorylation and crystal structures of
PAK4-peptide complexes suggested that phosphoacceptor residue preference is not
mediated by stronger binding of the favored substrate. Rather, favored
kinase-phosphoacceptor combinations likely promote a conformation optimal for
catalysis. Understanding the rules governing kinase phosphoacceptor preference
allows kinases to be classified as serine or threonine specific based on their
sequence.
|
|
|
|
|
|
|
