1. The CHIME Site at the University of Massachusetts
2. Section #1:  Hemoglobin and Heme

a. Viewing the molecule

i. Tranlate
ii. Rotate
iii. Roll
iv. Zoom

b. Using the menu to display the molecule

i. Rotation
ii. Display
iii. Color
iv. Select

c. The other buttons in this section of the tutorial

a. Alpha Helix
b. A rainbow coloring scheme from the N-terminus to the C-terminus helps to discern the separate alpha helices.
c. This is a cartoon representation.
d. We'll focus on a single alpha helix. This helix is at the protein-water interface.
e. Here is the isolated alpha helix.
f. The backbone representation connects alpha carbon positions in this alpha helix. These lines do not represent the positions of any actual chemical bonds.
g. Here are the actual bonds of the alpha helix backbone: three atom repeats of nitrogen, alpha carbon, carboxy carbon.

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, click on "Hemoglobin & Heme"
• In the right frame you should now see a set of buttons.   Click on the "X" button opposite "The hemoglobin molecule is made up of four polypeptide chains ...."
• This should load a rotating model of the hemoglobin molecule in the left frame.  In the right frame is a tutorial on "HEMOGLOBIN & HEME"

Hemoglobin and Heme

The rotating model of hemoglobin shows several things:

• It is composed of four separate chains of amino acids (polypeptides).  Each polypeptide is displayed in a different color.
• Each polypeptide binds one heme group which is displayed in red.

• Translate X or Y (moved left or right; up or down).  with the mouse by holding down the control key and the right button on the mouse.
• Rotate.  The image can be yawed (rotated left and right about the Y axis ) or pitched (rotated up or down about the X axis)  with the mouse by holding down the left button on the mouse.
• Roll.  The image can be rolled about the Z axis with the mouse by holding down the shift key and the right button of the mouse.
• Zoom.  The image can be resized with the mouse by holding down the shift key and the left button on the mouse.

• Rotation:  This function can be toggled on or off.
• Display:   The "Display" menu allows us to view different aspects of the structure:
1. Hold down the right mouse button.  Choose "Display" --- "Spacefill" --- "Van der Waals  Radii".
2. Resize the molecule by holding down the shift key and the left mouse button.  Move the mouse up or down to zoom in or out.  Reduce the molecule to the height of your window.
3. Manipulate the molecule with your mouse to stand it up vertically.
4. Hold down the right mouse button.  Choose "Options" --- "Rotation".
5. Click on "X  Spin".
6. Hold down the right mouse button.  Choose "Options" --- "Stereo Display".

 
• Reset:   Click on the "X" button opposite "The hemoglobin molecule is made up of four polypeptide chains ...."

• Color:   The following options are available for color display.  Play with them.
• Monochrome - self explanatory
• CPK (carbon grey; hydrogen white; oxygen red; nitrogen blue; phosphorus gold)
• Amino Acid - every amino acid is displayed in a different color
• Shapely - the amino acids are displayed according to the chemical properties of their side chains
• Group - this emphasizes the different elements of secondary structure and the ends of each polypeptide chain.  It is most useful when used in the "ribbon" or "cartoon" display mode.
• Chain - each of the polypeptide chains is displayed in its own color
• Structure - this emphasizes the different secondary structures.  Alpha helix is displayed in rose; beta pleated sheet in gold; random coil in thin blue/white lines.  It is most useful when used in the "ribbon" or "cartoon" display mode.
• Temperature and User:  not useful for our purposes

The Select function allows us to display different parts of the molecule in different ways.

We know that proteins have shape because it is necessary for them to bind something in order to perform their function.  For example and enzyme has an active site into which the substrate fits.  More generally we refer to these as the binding site on the protein and the ligand which fits into it.

In Hemoglobin we can display the protein chains and the ligand (the Heme group) in different ways.   We can display hemoglobin to emphasize the shape of the binding site:

• Hold the mouse button down.  Go to Select; then go to Hetero; then go to Ligand ("hetero" refers to any other atoms and molecules which are not part of the polypeptide chains).
• Go to the Color menu and select "CPK"
• Go back to Select;  then go to Protein.
• go to the Display menu and select "Wireframe"
• You should now see something like this.

The other buttons in this section of the tutorial:
 

  Each chain holds a heme group containing one Fe++ atom.

  The heme-iron complexes are colored red because they give hemoglobin its red color.  Actually, it is the yellow colored atom in the center which gives the Heme group the red color.  This atom is Iron. Heme has a red color because oxidized iron (rust) is red!  This is also why oxygenated blood is red.

  Now the heme molecules have been colored by element.  The Heme groups displayed using CPK colors.

  Spacefill view of atoms that make up a single heme molecule.  The Heme group displayed to show the true size of each atom, and the real shape of the molecule.

  Here is how iron is attached to the rest of the heme molecule.

  An elemental oxygen molecule binds to the ferrous iron atom in the lungs where oxygen is abundant, and is released later in tissues which need oxygen. Note that there is a difference between a single oxygen atom and an Oxygen molecule which is composed of two oxygen atoms!

  The position of bound elemental oxygen in one chain of hemoglobin.

  Space occupied by the heme bound oxygen in the polypeptide chain.

  A histidine nitrogen binds to the iron, helping to anchor its position. Don't worry about this one!

  A spacefill view (with the exception of the heme molecule) of the hemoglobin polypeptide chain.  This view shows a stick model of the Heme group with the yellow colored iron atom in the center.  The molecules on either side displayed in spacefill mode and CPK color are the side chains of 2 amino acids in the protein chain.

• Hold down the button on your mouse and go to the Options menu.  At the bottom choose Stereo Display.  Adjust the size to look something like this.
• Put your nose close up to the screen, and move slowly backward concentrating on the "third" image in the center.  At some point the image should appear 3 dimensional!  This view gives you a good idea of how closely ligands fit into binding pockets  .......... and how important SHAPE is to FUNCTION!!!

Secondary Structure

Click on the link for "Hemoglobin Secondary Structure".

Most of the amino acids in hemoglobin form alpha helices.

When you click on the "X" button, the rotating model of the hemoglobin molecule will load again.  Stop the rotation so you can view the molecule easily.  What you see is one of the four polypeptides and a single heme group (the author does not specify whether this is an a or b globin chain).
 

The segments of the amino acid chain which fold into a helix are shown in red.  Random coil (the segments which do not fold into a helix) are shown in white.  Start the rotation again so you can see the overall 3D structure.
 

  A rainbow coloring scheme from the N-terminus to the C-terminus helps to discern the separate alpha helices.

This coloring scheme helps to trace out the chain from the beginning which is colored blue -- light blue -- teal -- green -- yellow -- orange -- red, which is the end.

• Where is the a helix?
• Where is the Random Coil?

• Where is the a helix?
• Where is the Random Coil?

  Here is the isolated alpha helix.

  The backbone representation connects alpha carbon positions in this alpha helix. These lines do not represent the positions of any actual chemical bonds.

  Here are the actual bonds of the alpha helix backbone: three atom repeats of nitrogen, alpha carbon, carboxy carbon.

Stop the rotation.  Use the mouse to manipulate the molecule into a vertical position.  Reposition the model to the center of your window.  Resize the model so that the entire length fits in your window.  Using the mouse menu go to Color; then Amino Acid.  Now you can see the individual amino acids in the chain which is coiled into the a helix.

• How many amino acids are in this short polypeptide?

  Hydrogen bonds (white) stabilize the alpha helix.  Don't worry about this one.  View it if you are interested.
 

  The sidechains on the alpha carbons are shown.   Don't worry about this one.  View it if you are interested.

  Now the sidechain elements are identified:  C H O N  Don't worry about this one.  View it if you are interested.
 
 

Summary

Review
 
 
 

Protein Structure	amino acids	primary structure	secondary structure	tertiary structure	quaternary structure
Protein Function	Structure, SHAPE, and Function of Tools	Structure, SHAPE, and Function of Proteins	Arabinose Transporter	Hexokinase