Amino Acids

CARBON CENTRAL

When they mention carbon-based life forms, many characters in books, movies, and TV shows such as Star Trek are referring to the central role played by carbon atoms in life on Earth. There is no better example of what carbon-based means than amino acids.

All amino acids are built around a central carbon atom called the a carbon (abbreviated Ca). All amino acids have the same three chemical constituents bound to Ca: an amino group (NH3+), a carboxyl group (COO), and a hydrogen atom (white). The fourth group bound to Ca varies from amino acid to amino acid and is known as the R group or the side chain (here represented by the purple atom). The side chains give each amino acid its particular character, which influences the chemical and physical properties of the protein that contains it.

At pH 7.4 (the pH of human blood and most tissues, called physiological pH), amino acids are zwitterions, that is, ions that are simultaneously both positively and negatively charged. The amino group of amino acids carries a positive charge due to the presence of a proton, and the carboxyl group carries a negative charge due to the loss of a proton. These two charged groups account for the name amino acid.

AMINO ACID CATEGORIES

The 20 amino acids can be classified into categories according to the chemical properties of their R groups. Here, we classify them as hydrophobic, polar, and charged.

It's handy to remember which group each amino acid belongs to, so that you can anticipate the role an amino acid might play in the structure or function of a protein. If you learn the structures of the individual amino acids, you will enhance your understanding even further.

Hydrophobic amino acids

The side chains of the hydrophobic amino acids are nonpolar and cannot form hydrogen bonds with water or other polar entities. For this reason, hydrophobic side chains tend to be located on the inside of soluble proteins, protected from water. In proteins embedded in membranes, hydrophobic side chains are found on the outside of the protein in positions where they can interact with the nonpolar tails of membrane lipids.

Within the hydrophobic amino acid group, side chains vary in size and shape. Four of the hydrophobic amino acids, alanine, valine, leucine, and isoleucine, have side chains that are branched or unbranched hydrocarbon chains.

Use the Chime menu (right button click on the structure for PC, click-and-hold for Mac) to change these amino acids between the structural representations commonly used in molecular displays. Note that Stick representations emphasize the covalent bonds that form the skeleton of a molecule. Spacefill shows the space each atom occupies but obscures the bonds. Ball & Stick is a compromise between the latter two display styles. Toggle Hydrogen removes or replaces the hydrogen atoms of the structure to simplify it. Toggle Dots adds or removes the Spacefill dimension in a form that allows you to see the covalent bonds as well as the spacefilling dimension.

One of the four remaining hydrophobic amino acids, phenylalanine also has a purely hydrocarbon side chain like the previous four amino acids, but it is a ring structure rather than a chain. Methionine and tryptophan both contain an atom that can form a hydrogen bond, but the bulk of their side chains are nonpolar and therefore hydrophobic. Proline is unlike any other amino acid in that its nonpolar side chain doubles back to form a covalent bond with its amino group. This geometry causes a small kink in a polypeptide chain wherever a proline appears.


Review question 1

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Click on the one atom in each of the side chains of methionine and tryptophan that can form hydrogen bonds. For each selection, click on the atom and press the "Enter Selection" button next to the amino acid listed:

MET
TRP

When you are satisfied with both of your selections press .

Need a hint?


Review question 2

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Click on the Ca of Proline.

When you are satisfied with your selection press .

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Polar amino acids

The side chains of polar amino acids readily form hydrogen bonds. Polar side chains are likely to end up on the surface of a water-soluble protein, where they participate in hydrogen bonding with water, but they can also be buried in the protein interior if hydrogen-bonding partner(s) are internally available.

The amino acids serine, threonine, and tyrosine all have hydroxyl groups, which are classic hydrogen-bond donors.

Asparagine and glutamine each have an amide group, which can participate in hydrogen bonding.

Histidine and cysteine are both versatile amino acids. Histidine has a polar imidazole ring, which can accept or donate a proton in acid-base catalysis. The histidine ring's pKa of 6.5 can be influenced by nearby residues in a protein and can approach physiological pH. When pH and pKa are close, protons can more readily be donated or accepted. Histidine can therefore act as an acid or a base depending on its immediate environment, making it valuable in catalysis.


Review question 3

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Click on the hydrogen atom of histidine that can play a role in acid-base catalysis.

When you are satisfied with your answer press .

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Cysteine's thiol group can be oxidized to form a disulfide bond with a second cysteine side chain. This forms a covalent link between the two sulfur atoms of the cysteine side chains. Disulfide bonds help stabilize the folded shapes of some proteins and can also covalently link two separate protein chains.

Why are no hydrogen atoms shown in this structure? Hydrogen atoms are frequently omitted from molecular structures for two reasons. First, the most common method of structure determination for proteins, X-ray crystallography, does not detect the positions of hydrogen atoms. Second, hydrogen atoms are so numerous in larger molecules that they significantly complicate a structure and so may be purposely omitted from a display for clarity. This cystine was taken from a large protein whose structure was determined by X-ray crystallography.

Small, simple glycine is characterized as polar by default, since it lacks either a hydrophobic or charged side chain. Glycine's side chain is hydrogen, making it the only amino acid that does not have four different chemical groups attached to Ca.

Charged amino acids

Amino acid side chains that are charged almost always appear on the surface of a protein where they can interact with water or with polar or ionic solutes. They are found buried in the protein's interior only when an oppositely charged group or ion is available nearby, so that both charges are neutralized. At physiological pH, four amino acid side chains are always charged: aspartate and glutamate (negative) and lysine and arginine (positive).

As you have seen, the side chains of the 20 amino acids provide a variety of sizes, shapes, and chemical functionality. Proteins harness the features of amino acids for many structural and catalytic tasks. But keep in mind that some amino acids are also used for purposes other than building proteins. For example, the amino acid glutamate is a signaling molecule in the brain, that is, a neurotransmitter. Next we'll look at how amino acids are bound together into chains that make up proteins.

PEPTIDE BONDS LINK AMINO ACIDS TOGETHER

Amino acids in a chain are covalently linked via peptide bonds, which form between the carboxyl group of one amino acid and the amino group of the next.

This short chain is only two amino acids long, so it is called a dipeptide. When linked by a peptide bond, an amino acid is called a residue. A dipeptide has two residues. By convention, a chain of amino acids begins with the positively charged amino end of the chain (nitrogen in blue) and ends with a negatively charged carboxyl group (oxygen in red).


Review question 4

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Amino acid residues in a chain are numbered consecutively from the beginning of the chain to the end. Click on the Ca of amino acid #1 in this dipeptide.

When you are satisfied with your answer press .

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Short chains of amino acids are often referred to by the number of amino acids in the chain: dipeptide, tripeptide, etc. As the length of the chain gets longer, we are more likely to refer to it as a polypeptide, "poly" meaning "many." The continuous chain of atoms from which the side chains project is known as the backbone (pulsing blue) of the polypeptide. The chain of the backbone has a distinct repeating pattern, starting from the amino end, of three atoms:

N–Ca–C–N–Ca–C–N–Ca–C…

The carbonyl oxygen atoms are also considered part of the backbone.

In many polypeptide displays (including this one), the Ca atoms are visibly connected to three groups: the side chain, an amide nitrogen, and a carbonyl carbon. The fourth "group" that all Ca are connected to, hydrogen, is not shown, for the same reasons discussed above.


Review question 5

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In all polypeptides displayed without hydrogen atoms, one type of amino acid residue appears to have no side chain at all. Which one is it?

Enter the three-letter designation for this amino acid below.

Answer:

Then click on this amino acid in the structure.

When you are satisfied with both your answer and selection press .

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Review question 6

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Recall the numbering scheme for residues in a polypeptide, and click on the Ca of the fourth residue in the chain.

When you are satisfied with your selection press .

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PEPTIDE CHAINS

Flexibility within limits

In a peptide bond, there is a partial sharing, or resonance, of two pairs of electrons between the carbonyl carbon and the amide nitrogen. Therefore, both the peptide bond and the bond to the carbonyl oxygenhave some double-bond character.

This electronic structure prevents rotation around the peptide bond. However, rotation can occur around both bonds involving Ca, so the polypeptide chain can twist and turn considerably at those points. In addition, rotation occurs around the bonds in the amino acid side chains.

Each of these polypeptides has the same number of residues, and yet they adopt very different shapes or conformations, depending on the degree of rotation around each Ca.


Review question 7

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One of these two polypeptides contains a proline residue. Click on its Ca.

When you are satisfied with your selection press .

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You have completed this exercise.

You can explore the types of twists and turns that give proteins their characteristic conformations in the next exercise, Protein Secondary Structure.