 |
PDBsum entry 1h4l
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Kinase/kinase activator
|
PDB id
|
|
|
|
1h4l
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
* Residue conservation analysis
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Structure and regulation of the cdk5-P25(nck5a) complex.
|
|
|
Authors
|
|
C.Tarricone,
R.Dhavan,
J.Peng,
L.B.Areces,
L.H.Tsai,
A.Musacchio.
|
|
|
Ref.
|
|
Mol Cell, 2001,
8,
657-669.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
CDK5 plays an indispensable role in the central nervous system, and its
deregulation is involved in neurodegeneration. We report the crystal structure
of a complex between CDK5 and p25, a fragment of the p35 activator. Despite its
partial structural similarity with the cyclins, p25 displays an unprecedented
mechanism for the regulation of a cyclin-dependent kinase. p25 tethers the
unphosphorylated T loop of CDK5 in the active conformation. Residue Ser159,
equivalent to Thr160 on CDK2, contributes to the specificity of the CDK5-p35
interaction. Its substitution with threonine prevents p35 binding, while the
presence of alanine affects neither binding nor kinase activity. Finally, we
provide evidence that the CDK5-p25 complex employs a distinct mechanism from the
phospho-CDK2-cyclin A complex to establish substrate specificity.
|
|
|
|
|
|
|
|
Figure 2.
Figure 2. Comparison of p25 and Cyclin A
|
|
Figure 6.
Figure 6. Role of Glu240
p25
in Substrate Recognition
|
|
|
|
|
|
The above figures are
reprinted
by permission from Cell Press:
Mol Cell
(2001,
8,
657-669)
copyright 2001.
|
|
|
|
|
|
|
