Substance X putative site of action

 In order to see the 3-D structures presented in this section, you have to instal the CHIME plugin.

During this tutorial we tried to elucidate the mechanism by which Substance X arrests the cell cycle.
 

The structure of CDK2 in the presence or absence of cyclin A and p27 was determined experimentally.   We will now examine the interactive structural models of these 3-D structures to view the putative site/s of action of Substance X.

To examine the interactive structural models click here. (This will open a new window.)
Follow this tutorial from beginning to end.

To learn more about the 3-D structure of CDK2 click here.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Old version

From this stage on you'll have to use two windows simultaneously: one to read the instructions, and another to inspect the 3-D structure of CDK2 + cyclin A discussed here. Reuce the size of this window.
To open a second window presenting the 3-D structure, follow this link.
Wait till this page is fully loaded!
Examine the 3-D structure ofCDK2 + cyclin A. Chains A and C are CDK2 (residues 1-298). Chains B and D are a truncated form of cyclin A (residues173 - 432).We will focus on chains A and B.

Go to the "Structural Waters" menu in the top window on the right and click on the HOH OFF option.
Go to the menu "Basic Structure Presentation" in the top window on the right and click on COLOR BY CHAIN option. The chains appear in a wireframe form and the ligand (ATP) appears in a spacefill form.
Using the left button of the mouse rotate the molecule so you can see the ligand more clearly.
Press SHIFT in your left hand and drag the mouse while pressing the left button using your right hand - this will enlarge the 3-D structure.

First, we will highlight those residues in CDK2 which are involved in cyclin binding.
Go to the bottom window. Follow the sequence of chain A and click on the buttons below the following residues:
R36 ; D38 ; E40 ; E42 ; P45 ; S46 ; T47 ; A48 ; I49 ; R50 ; E51 .
Click on COLOR BY CHAIN and rotate the molecule if necessary.

Now we will highlight those residues in cyclin A which are involved in CDK2 binding.
Go to the bottom window. Follow the sequence of chain B and click on the buttons below the following residues:
L263 ; K266 ; F267 ; E295 ; L299 ; L306 ;
Click on COLOR BY CHAIN and rotate the molecule if necessary.

To examine an interactive structural model of the 3-D structure of CDK2 click here. (This will open a new window.)