Figure 5.
Figure 5. The CDK2–Cyclin A–CksHs1 Ternary Complex(A)
Ribbon diagram of a CDK2–cyclin A–CksHs1 complex model based
on the coordinates of our CDK2–CksHs1 complex and those of a
CDK2–cyclin A complex ([30]) in which the two CDK2 molecules
were superimposed based on the Cα atoms of the C-lobe. Besides
two distinct binding sites for cyclin A and CksHs1 at the
molecular surface of CDK2, this model reveals a large
bowl-shaped groove centered around the phosphorylation site at
Thr-160 (middle) in the activated conformation of the CDK2 T
loop and bordered by cyclin A and CksHs1 molecules. The presence
of positively charged residues (Lys-24, Lys-30, and Lys-34 in
CksHs1 and Lys-226 and Lys-417 in cyclin A) located on each side
of the groove is displayed (purple bonds and blue for nitrogen
atoms as balls). The molecules and the functionally important
elements in CDK2 are color coded as in Figure 1B, with cyclin A
in green. ATP is taken from the CDK2–cyclin A complex
coordinates previously described ( [30]).(B) Molecular surface
of the CDK2–cyclin A–CksHs1 complex oriented vert,
similar 90° away from that in (A), with the same color code.
The CksHs1 phosphate anion–binding site (blue) is exposed into
the solvent and located on the same side of the CDK2 catalytic
site with the ATP molecule bound between the two lobes, thus
forming a continuous surface for recognition of a Cdk substrate
or other phosphoproteins. The two CksHs1 α helices (orange) are
also solvent accessible. The T loop (white), containing the
phosphorylation site at position Thr-160 (middle), protrudes at
the interface of CksHs1 and cyclin A. Figure 1 and Figure 2 and
2B, 3C, and 4 were generated with the Application Visualization
System (AVS) (Advanced Visual Systems, Waltham, Massachusetts),
and Figure 1A and Figure 2C were generated with TURBO-FRODO (
[52]). The solvent-accessible surfaces were calculated with MS (
[9]), and the ribbon diagrams were generated using RIBBONS (
[8]) implemented in AVS.
The above figure is reprinted
by permission from Cell Press:
Cell
(1996,
84,
863-874)
copyright 1996.
vert,
similar 90° away from that in (A), with the same color code.
The CksHs1 phosphate anion–binding site (blue) is exposed into
the solvent and located on the same side of the CDK2 catalytic
site with the ATP molecule bound between the two lobes, thus
forming a continuous surface for recognition of a Cdk substrate
or other phosphoproteins. The two CksHs1 α helices (orange) are
also solvent accessible. The T loop (white), containing the
phosphorylation site at position Thr-160 (middle), protrudes at
the interface of CksHs1 and cyclin A. Figure 1 and Figure 2 and
2B, 3C, and 4 were generated with the Application Visualization
System (AVS) (Advanced Visual Systems, Waltham, Massachusetts),
and Figure 1A and Figure 2C were generated with TURBO-FRODO (
[52]). The solvent-accessible surfaces were calculated with MS (
[9]), and the ribbon diagrams were generated using RIBBONS (
[8]) implemented in AVS.