Download Amino Acid Starter Kit

Proteins are large, linear polymers of amino acids
that spontaneously fold into complex 3D shapes.
Although protein structure appears to be very
complex, the chemical properties that determine
protein structure are relatively simple.
The Amino Acid Starter Kit© allows your students
to explore how the unique chemical properties of
the 20 amino acids determine the final shape of a
protein. Two Student Handouts lead your students through the hands-on activities.
Student Handout 1
A dual coloring scheme allows students to first
- group the different sidechains into one of five categories: hydrophobic (nonpolar), hydrophilic
(polar), negatively charged, positively charged, and
cysteine... and then flip the sidechain over to…
- examine the atoms that make up each sidechain to
learn how the different functional groups determine the chemical properties of amino acids.
Your students will then attach sidechains to a mini-toober and fold it into a
15-amino acid protein, following the chemical properties of the sidechains.
As they fold their proteins your students will soon discover that it is easy to
find a 3D shape in which all of the hydrophobic sidechains are on the inside
of their globular structure. As they continue to fold their protein, applying
each additional property, it becomes increasingly difficult to find shapes
that simultaneously satisfy all of the properties.
Following this engaging, hands-on protein folding activity, your students
will have a basic understanding of how the physical and chemical properties
of amino acids determine protein structure. They also will be ready to begin
a more thorough exploration of molecular structure using the computer
visualization tools that are included on the CD accompanying this kit.
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Introduction - Page 1
Student Handout 2
In the first set of activities in this kit, Discovering the Properties of Amino Acids and Folding a 15-Amino Acid
Protein, your students explored the primary and tertiary structure of proteins, including the role of the amino
acid sidechains in determining the overall shape of a protein. The second set of activities in the kit explores the
secondary structure of proteins.
Simple tools allow students to explore:
- the alpha helix and beta sheet are the two primary elements of secondary
structure.
- hydrogen bonds in alpha helices and beta sheets stabilize protein structures
- the alpha helix and the beta sheet represent different ways to optimize the
hydrogen bonding that can occur between the amino nitrogen of one amino
acid and the carbonyl oxygen of another
- although a single hydrogen bond is weak, multiple hydrogen bonds in the
alpha helix and beta sheet contribute significantly to the stability of
molecular structures
- the alpha helix and beta sheet are features of the backbone atoms
Using the mini-toobers – and their fingers as bending jigs – your students will form a beta sheet and stabilize it
with hydrogen bond connectors. Then they will form an alpha helix and stabilize it with hydrogen bond connectors. Then with a couple of folds, you students will make a Zinc Finger and learn about its function.
The computer visualization tools on the CD (included with the kit) will allow your students to begin a
more thorough exploration of the Zinc Finger.
National Standards
National Content Standard A: Science as Inquiry
Scientific explanations must adhere to criteria such as:
- a proposed explanation must be logically consistent;
- it must abide by the rules of evidence; it must be open to questions and possible
modification;
- it must be based on historical and current scientific knowledge.
National Content Standard C: Life Science Standards
Students should understand:
- the chemical basis of life;
- Inside the cell is a concentrated mixture of thousands of different molecules;
- Most cell functions involve chemical reactions;
- Smaller precursor molecules (subunits) can be used to assemble larger molecules with
biological activity, including proteins.
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Introduction - Page 2
Amino Acid Starter Kit Contents
1
Magnetic Chemical Properties Circle
1
Laminated Amino Acid Sidechain List
21
Magnetic Amino Acid Sidechains (1 each of the 20 Amino
Acids plus 1 additional cysteine)
1
4’ Mini-Toober
15
Metal Mini-Toober Clips
120
CPK Coloring Dots
6
Hydrogen Bond Connectors
1
CD with Teacher Notes, Student Handouts and Jmol Visualization Tools
Please contact us if any part are missing or damaged.
CD Contents
Introduction, National Standards, and Contents
Teacher Notes
Student Handout 1
Student Handout 1 Key
Student Handout 2
Student Handout 2 Key
Toober Variations
Toober Variations Key
Read Me First (for Jmol and PDF information)
Amino Acids Jmol*
Basic Principles of Chemistry that Drive Protein Folding Part 1 Jmol*
Basic Principles of Chemistry that Drive Protein Folding Part 2 Jmol*
Zinc Finger Jmol*
Word Files (PC)*
Photo Files*
Center for BioMolecular Modeling Tertiary and Quaternary Protein Structure, Lesson 6
Please note that most of the files are PDFs for universal viewing and printing. (A link is provide to download Adobe Acrobat Reader (free software) for those who don’t have it installed.) We also provide Word
(PC) and photo files for teachers who want to develop their own student handouts or worksheets. (If you
have trouble opening the Jmol files, please consult with your school IT staff.)
* Jmol files developed by John Regner
CAUTION: This product should be kept out of the reach of children under the age of 3, because the molecules or their pieces may present
a choking hazard to small children. This is a science education product, not a toy. It is not intended for children under 8 years old.
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Introduction - Page 3
Amino Acids - Building Blocks of Proteins
Amino Acids are small molecules used by cells to make proteins.
There are 20 Amino Acids and each one consists of two parts — a Backbone and a Sidechain. The
backbone is the same in all 20 Amino Acids and the sidechain is different in each one.
Each sidechain consists of a unique combination of atoms which determine its 3D shape and its chemical
properties.
When different amino acids join together to make a protein, the unique properties of each amino acid
determine how the protein folds into its final 3D shape. The shape of the protein makes it possible to
perform a specific function in our cells.
The activities described in this handout primarily focus on amino acid sidechains. They will help you
understand how the unique properties of each sidechain contribute to the structure and function of a
protein.
1. First, look at the components in your
Amino Acid Starter Kit. Make sure
you have:
- Chemical Properties Circle
- Amino Acid Chart
- Mini-Toober (foam-covered wire)
with one Blue End Cap and
one Red End Cap
- 21 Foam Amino Acid Sidechain
Models with Magnets
- 15 U-shaped Metal Clips
- Red, Blue, Yellow, Green and
White Dots
- Hydrogen Bond Connectors
Photo shows the Three-Group Amino Acid Starter Kit.
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All Rights Reserved. U.S. Patents 6,471,520B1; 5,498,190; 5,916,006; other U.S. and International Patents Pending.
Student Handout 1 Key - Page 1
Chemical Properties Circle & Amino Acid Chart
2. Place each foam amino acid sidechain on the magnetic Chemical Properties Circle according to its
chemical properties. The sidechains are colored to reflect their chemical properties according to
the following coloring scheme:
Hydrophobic Sidechains are
Hydrophilic Sidechains are
Acidic Sidechains are
Basic Sidechains are
Cysteine Sidechains are
You will need to consult the Amino Acid Sidechain List in your
kit (photo above) to find the name of each sidechain, so you
can position it correctly on the circle.
3. After each sidechain has been correctly positioned
on the circle, you should add the colored dots to the
gray side of each sidechain to color code the atoms
that make up each sidechain. Use the amino acid
sidechain list in your kit. Scientists established this
CPK Coloring Scheme to make it easier to identify
specific atoms in models of molecular structures.
Carbon is
Oxygen is
Nitrogen is
Hydrogen is
Sulfur is
CPK Coloring Scheme
4. After placing the correct dot(s) on each sidechain, return each one to its place
on the circle. Position the circle so you can easily read the names. (See the circle photos above.)
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Student Handout 1 key - Page 2
Chemical Properties Circle (continued)
Turn all of the sidechains so that the colored side (yellow, white, red, blue) of each one is facing you
as you read the names of the sidechains. (Photo on left)
Now rotate the circle so that the names of the sidechains are upside down and the gray side of each
sidechain is facing you. (Photo on right)
Examine the sidechains and their positions on the circle.
Describe Your Observations
Explain what you observed:
- Do you see similarities or patterns in the sidechains? ______________
Yes
Hydrophobic amino acids are composed primarily of gray carbons.
________________________________________________________________________
Acidic amino acids have oxygen-containing sidechains.
________________________________________________________________________
Basic amino acids have nitrogen-containing sidechains and
________________________________________________________________________
Hydrophilic amino acids have a mixture of oxygen and nitrogen.
_______________________________________________________________________
carbon
- Hydrophobic sidechains are composed primarily of ___________________________
atoms.
oxygen
- Acidic sidechains contain two _________________
atoms. This is called a carboxylic acid functional group.
- Basic sidechains contain _________________________
atoms. This is called an amino functional group.
nitrogen
- Hydrophilic sidechains have various combinations of ________________________________________
oxygen, nitrogen and sulfur
________________________________________________________________________
_______________________________________________________________________.
- a hydrophobic amino acid that contains a nitrogen atom.
- An exception to the above observation is: Tryptophan
________________________________________________
_______________________________________________________________________
- Optional Activity - Amino Acids Jmol (See CD or Amino Acid Starter Kit© resources on website)
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Student Handout 1 Key - Page 3
Folding a 15-Amino Acid Protein
Once you have explored the chemical properties and atomic composition of each sidechain, you are
ready to predict how proteins spontaneously fold up into their 3D shapes.
Predicting What Causes Proteins to Fold into their 3D shapes
- From your experience with oil and water, which sidechains might position themselves on the interior of a
protein, where they are shielded from water? _______________________________________
The hydrophobic amino acids - Tryptophan, Leucine, Isoleucine, Valine, Proline, Alanine
_______________________________________________________________________
and Glycine.
_______________________________________________________________________
- From your experience with magnets or electricity, which sidechains might be attracted to each other?
_______________________________________________________________________
The basic amino acids (+ charge) and the acidic amino acids (- charge).
_______________________________________________________________________
_______________________________________________________________________
_______________________________________________________________________
- Would the final shape of a protein be a high energy state or a low energy state for all of the atoms in the
structure? ________________________________________________________________
A low energy state.
Why? __________________________________________________________________
A low energy state is more stable than a high energy state.
_______________________________________________________________________
_______________________________________________________________________
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Student Handout 1 Key - Page 4
Folding a 15-Amino Acid Protein (continued)
1. Unwind the 4-foot Mini-Toober (foam covered wire) that is in your kit. Notice the blue and red end
caps on the ends of your mini-toober. The blue end cap represents the N-terminus (the beginning)
of the protein, and the red end cap represents the C-terminus (the end) of the protein.
2. Select 15 metal u-shaped clips from your kit. (A spare clip is usually shipped with each kit.) You will
also need a ruler.
Beginning at the N-terminus of your mini-toober, measure about three inches from the end of your
mini-toober and slide the first clip into place there. (See photo below.)
Place the rest of the clips three inches apart on your mini-toober until all 15 are attached to the minitoober.
Find the part of the drawing that represents the backbone section of the amino Acid. What do
you think the clips represent?
_____________________________________________________________
The alpha-carbon, because this is the atom that the sidechains are bonded to.
_____________________________________________________________
_____________________________________________________________
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Student Handout 1 Key - Page 5
Folding a 15-Amino Acid Protein (continued)
3. Select methionine from the chemical properties circle and place
it on the clip closest to the blue end cap.
Choose any other sidechains from the chemical properties circle as long as you have the right number of each color, as indicated in the chart to the right.
Mix the Sidechains together and place them (in any order you
choose) on your mini-toober.
The sequence of Amino Acid Sidechains that you determined when placing them on the mini-toober is called the Primary Structure of your
protein. As a general rule the final shape of a protein is determined by
its primary structure (the sequence of its Amino Acids).
4. Now you can begin to fold your 15-amino acid protein according to the chemical properties of its
sidechains. Remember all of these chemical properties affect the protein at the same time!
- Start by folding your protein so that all of the hydrophobic sidechains are buried on the
inside of your protein, where they will be hidden from polar water molecules.
- Next, fold your protein so the acidic and basic (charged) sidechains are on the outside surface of the protein and pair one negative sidechain with one positive sidechain so that
they come within one inch of each other and neutralize each other. This positive-negative
pairing helps stabilize your protein.
- As you continue to fold your protein to apply each
new property listed below, you will probably
find that some of the sidechains you previously
positioned are no longer in place. For example,
when you paired a negatively charged
sidechain with a positively charged one, some
of the hydrophobic sidechains probably move
to the outer surface of your protein. Continue
to fold until the hydrophobic ones are buried
on the inside again. Find a shape in which all
the properties apply.
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Student Handout 1 Key - Page 6
Folding a 15-Amino Acid Protein (continued)
- Continue to fold you protein making sure that your polar sidechains are also on the outside surface of your protein where they can hydrogen bond with water.
- Last, fold your protein so that the two cysteine sidechains are positioned opposite each other on
the inside of the protein where they can form a covalent disulfide bond that helps stabilize
your protein.
The final shape of your protein when it is folded is called the Tertiary Structure.
- Why should Methionine be next to the Blue End Cap?
Because all proteins begin with Methionine - and protein synthesis begins at
_________________________________________________________________
the N-terminal end of a protein.
_________________________________________________________________
- What happened as you continued to fold your protein and applied each new chemical property to
your protein? _______________________________________________________
It became more compact and more complicated.
_________________________________________________________________
_________________________________________________________________
_________________________________________________________________
- Were you able to fold your protein, so that all of the chemical properties were in effect at the same
Yes. (Note to teachers: some students may answer “No”.)
time? ____________________________________________________________
_________________________________________________________________
- If not, do you have any ideas why you weren’t able to fold your protein in a way that allowed all of
the chemical properties to be in effect simultaneously? ___________________________
Some sequences simply do not allow for a single shape that simultaneously satis_________________________________________________________________
fies all the principles of chemistry that drive protein folding.
_________________________________________________________________
_________________________________________________________________
No.
- Did your protein look like the proteins other students folded? __________________________
Explain. __________________________________________________________
Because everyone had a different sequence of amino acids.
_________________________________________________________________
_________________________________________________________________
_________________________________________________________________
- How many different proteins, 15 amino acid long, could you make given an unlimited number of
each of the 20 amino acids? _____________________________________________
2015 = 3.28 x 1019
_________________________________________________________________
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Student Handout 1 Key - Page 7
15-Amino Acid Protein Questions (continued)
-Most real proteins are actually in the range of 300 amino acids long. How many different possible
proteins, 300 amino acids in length, could exist?
_________________________________________________________________
20300 = 2 x 10390
_________________________________________________________________
_________________________________________________________________
-How many different proteins are found in the human body? (Another way to ask this question is —
How many different genes are there in the human genome?)
Approximately 50,000 or 5 x 104
_________________________________________________________________
_________________________________________________________________
- Assuming that all human proteins are 300 amino acids long,
what fraction of the total number of possible different
proteins is found in the human body?
_______________________________________
2 x 10-386 = miniscule!
_______________________________________
_______________________________________
_______________________________________
_______________________________________
_______________________________________
- Why do you think there are fewer actual proteins than possible ones?
________________________________________________________________
Because only a relatively small number of amino acid sequences can adopt a
________________________________________________________________
stable shape that simultaneously satisfies all of the principles of chemistry.
________________________________________________________________
________________________________________________________________
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Student Handout 1 Key - Page 8
15-Amino Acid Protein Questions (continued)
This is the Primary Structure of your protein.
In the space below, sketch the Tertiary Structure of your protein.
The next student handout provides folding activities and information that will help you understand the
Secondary Structure of proteins.
- Optional Activity - Basic Priciples of Chemistry that Drive Protein Folding Part 1 Jmol
Basic Priciples of Chemistry that Drive Protein Folding Part 2 Jmol
(See CD or Amino Acid Starter Kit© resources on website)
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Student Handout 1 Key - Page 9
Secondary Structure
In the previous protein folding activity, you created a hypothetical 15-amino acid protein and learned
that basic principles of chemistry determine how each protein spontaneously folds into its 3-dimensional
shape. You learned that the sequence of amino acids in a protein (from N-terminus to C-terminus) is its
Primary Structure. The final folded, 3-dimensional shape of your protein is its Tertiary Structure.
In this second protein folding activity, you will now learn about the Secondary Structure of proteins. Secondary Structure consists of alpha helices and/or beta sheets. Proteins can be thought of as a
series of alpha helices and beta sheets, joined by loops of less regular protein structure.
An alpha helix is a compact
right-handed helix, with 3.6
amino acids per turn of the
helix. The amino acid
sidechains are bonded to the
alpha carbon of each amino acid
and radiate outward from the
helix. The alpha helix is stabilized by hydrogen bonds – weak
bonds between the amino nitrogen of one amino acid (x), and
the carbonyl oxygen of another
amino acid (x+4) located four
residues further along the chain.
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A beta sheet is an extended,
zig-zag structure in which
individual strands are positioned parallel or anti-parallel
to each other to form flat
sheets in proteins. Since the
amino acid sidechains are
bonded to the alpha carbons
of each amino acid, they are
alternately orientated above
and below the plane of the
sheet. The beta-sheet is stabilized by hydrogen bonds
between the amino nitrogen of
one amino acid and the carbonyl oxygen of another
amino acid in an adjacent beta
strand.
Student Handout 2 Key - Page 1
Folding a Toober Model of the Zinc Finger
In this activity, you will fold a model of the first of three zinc fingers of the Zif268 protein. The primary
structure of this zinc finger is:
The sidechains of the seven amino acids circled in the above sequence will be included in the model you
fold.
1. Primary Structure: Map the positions of the seven amino acids on the mini-toober. Since the
toober is 48 inches long, and the zinc finger is 28 amino acids long, each amino acid occupies 1.7
inches of toober. Using a ruler, measure the distances shown below, and add a labeled metal clip to
the toober at each position. Label the clip with an appropriately colored dot.
2. Secondary Structure: Fold the toober into its secondary structure. The first 13 amino acids (the
first 22 inches from the N-terminus) should be folded into a 2-stranded beta sheet. This can be made
by creating a zig-zag structure that is bent in the middle as shown in the photos below. You can also
add the plastic hydrogen bonds to your model as shown in the far right photo.
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Student Handout 2 Key - Page 2
Folding a Toober Model of the Zinc Finger (continued)
The last 14 amino acids of the zinc finger exist as a compact, right-handed alpha helix. This can be
made by wrapping the mini-toober around your finger to create four 360 degree turns as shown in
the photos below. Add the hydrogen bond connectors as shown in the far right photo.
Your mini-toober should now look similar to the one shown below.
3. Tertiary Structure: Fold the beta-sheet and alpha-helix into the final tertiary structure of the zinc
finger.
Add the seven amino acid sidechains to the clips on the toober. In its final tertiary structure, these
seven sidechains will be positioned such that:
- The two cysteine and two histidine sidechains will be oriented so that they can
simultaneously bind to a single zinc atom (not included in this kit) in the center of the
structure.
- The two hydrophobic amino acid sidechains phenylalanine (Phe, F) and leucine (Leu, L) will
be orientated toward the inside of the structure.
- The positively-charged arginine sidechain will be exposed at the top of the alpha helix, where
it is available to bind to the negatively-charged phosphate backbone of DNA.
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Student Handout 2 Key - Page 3
Folding a Toober Model of the Zinc Finger (continued)
As a folding guide, you can either use the photo shown below or the interactive Jmol image of a
zinc finger on the CD included in the Amino Acid Starter Kit.
Note: As you fold your toober, you may need to rotate the sidechains around the mini-toober to
make them adopt the desired final shape.
The zinc (not
included with the
kit) binds simultaneously to the two
histidines and two
cysteines.
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Student Handout 2 Key - Page 4
Folding a Toober Model of the Zinc Finger (Questions)
1. Both alpha helices and beta sheets are stabilized by hydrogen bonds.
- Which atoms share the hydrogen in these weak bonds?
The nitrogen of an amino group and the oxygen of a carbonyl group.
_________________________________________________________________________
_________________________________________________________________________
- Are these backbone atoms or sidechain atoms?
Backbone atoms.
_________________________________________________________________________
_________________________________________________________________________
2. Describe the secondary structural elements that comprise a zinc finger:
___________________________________________________________________
A 2-stranded beta sheet and a short alpha helix.
___________________________________________________________________
___________________________________________________________________
___________________________________________________________________
3. How is a zinc atom involved in the stabilization of the zinc finger motif?
The zinc atom is simultaneously bound by the 2 cysteine and the 2 histidine
___________________________________________________________________
sidechains.
___________________________________________________________________
___________________________________________________________________
___________________________________________________________________
4. Zinc fingers often bind to DNA. How might the arginine sidechain (positively-charged) shown on your model be
involved in DNA binding?
___________________________________________________________________
DNA has a negatively-charged phosphate backbone. Therefore, the positively___________________________________________________________________
charged arginine of the zinc finger can bind to DNA via an electrostatic interaction.
___________________________________________________________________
___________________________________________________________________
- Optional Activity - Zinc Finger Jmol (See CD or Amino Acid Starter Kit© resources on website)
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Student Handout 2 Key - Page 5