Sickle Cell Anemia is a genetic disease.  This means that it results from a damaged gene which then codes for a protein with a changed amino acid, which then folds incorrectly and has the wrong shape, and cannot function correctly. Sickle Cell Anemia is also referred to as a molecular disease, because we understand what is wrong at the level of cells and molecules.  The molecule which malfunctions is the b globin chain in hemoglobin  (remember that hemoglobin is composed of 4 amino acid chains or polypeptides - 2 a globin chains and 2 b globin chains). The b globin chain is a polypeptide of 146 amino acids.  In most people the 6th amino acid is glutamic acid.  However in people with sickle cell anemia glutamic acid has been substituted with valine.  This change .... of only one amino acid of the 146 .... causes sickle cell anemia,  which kills most children who suffer with it by the age of 20 years.

 
 

Go to the CHIME site at the University of Massachusetts.

• Click on:    "Hemoglobin. An introductory presentation suitable for lectures or individual study"

Click on:    "Hemoglobin ( user-controlled mode for lectures or self-paced study. Rotation can be stopped with Chime's Menu.) "
• Now you should see a black page with 2 frames.  In the right frame, towards the bottom, click on "Sickle Hemoglobin"
• Now you should see a  second black page with two frames. In the right frame you should now see a set of buttons.   Click on the "X" button opposite " Sickle hemoglobin differs from normal hemoglobin A by a single amino acid ........."
• This should load a rotating model of the hemoglobin molecule in the left frame.  In the right frame is a tutorial on "SICKLE HEMOGLOBIN"

Hemoglobin and Heme

  Sickle hemoglobin differs from normal hemoglobin by a single amino acid ...........

The rotating model looks like the normal hemoglobin we saw earlier.  However this is a variant of hemoglobin, which is found in people with sickle cell anemia.  Examine the model carefully noting the hydrophobic patches which are colored white.  After you have examined the model, and read the text:

• Hold down the right button on the mouse to get the menu.  Deselect "Rotation" to stop the rotation.
• On the menu go to SELECT; then HETERO;  then LIGAND
• On the menu go to DISPLAY;  then BALL & STICK.
• On the menu go to DISPLAY;  then SHAPELY.
• You should now see the Heme groups displayed as ball and stick models in magenta.  Using the mouse to manipulate the molecule, locate the white hydrophobic patches again.
• NOTE:  the hydrophobic patches which result from the substitution of the amino acid Valine for Glutamic Acid are not near the Heme groups!
• WHY are there two hydrophobic patches?

  When deoxygenated, a small hydrophobic patch ...........

• The hydrophobic patches which result from the substitution of the amino acid Valine for Glutamic Acid are not near the Heme groups!
• The normal hydrophobic patches  are near the Heme groups!

  The hydrophobic spots stick to each other (excluding water)  .......

• Go to SELECT; then PROTEIN; then PROTEIN (at the top of the menu).
• Go to DISPLAY;  choose WIREFRAME.
• Go to DISPLAY;  choose BACKBONE (farther down the menu).

• You should be able to see something like this.
• Now zoom in to see something like this:
• Go to the OPTIONS menu;  choose STEREO DISPLAY.  When you view it correctly you will see 3 panels; in the middle panel the 3 hydrophobic patches will appear to be 3D.  One of the hydrophobic patches on the blue polypeptide will be closest to you.  the other hydrophobic patch on the blue polypeptide, and the hydrophobic patch on the yellow polypeptide will be farther away.  However all 3 will be in close proximity to each other!