Ch. 3 Biology 161

you can determine which type of amino acid it is by asking three questions:

1. Does the R-group have a negative charge? If so, it is acidic and will lose a proton, like aspartate. 2. Does the R-group have a positive charge? If so, it is basic and will pick up a proton, like lysine. 3. If the R-group is uncharged, does it have an oxygen atom? If so, then the highly electronegative oxygen will form a polar covalent bond in the R-group, thus making it uncharged polar like serine. The overall polarity of an R-group is based on the number of highly polar covalent bonds relative to nonpolar bonds.

Summary table

1. The combination of primary, secondary, tertiary, and qua- ternary levels of structure is responsible for the fantastic diversity of sizes and shapes observed in proteins. 2. Protein folding is directed by the sequence of amino acids present in the primary structure. 3. Most elements of protein structure are the result of folding polypeptide chains.

enzyme

A protein that functions as a cat- alyst is called an

8.If proteins could fold only into rigid, inflexible structures, how might this affect the cell's ability to regulate their function?

A protein's activity is regulated by controlling when or where it is folded into its active form. Many proteins are in a flexible, inactive form until bound to molecules or ions. If proteins had only a single, inflexible folded conformation, this type of control could not occur.

Tertiary structure

A protein's distinctive three-dimensional shape, tertiary structures form using a variety of bonds and interactions between R-groups or between R-groups and the backbone. the overall folded shape of a complete polypeptide gives a protein its tertiary structure. this level of structure is stabilized by bonds and other interactions. (b) these different examples of tertiary structure include interactions between α-helices and β-pleated sheets (secondary structures).

hydrophilic

Both polar and electrically charged R-groups interact readily with water. They dissolve easily in water.

Ionic bonding

Ionic bonds may form between groups that have full and opposing charges, such as the ionized acidic and basic side chains

Hydrophobic interactions

In an aqueous solution, water molecules interact with the hydrophilic polar side chains of a polypeptide, forcing the hydrophobic nonpolar side chains to coalesce into globular masses. When these nonpolar R-groups come together, the surrounding water molecules form more hydrogen bonds with each other and the polar residues on the surface of the protein, increasing the stability of their own interactions and the disorder of the aqueous solution.

ionized form of amino acid

In water, which has a pH of 7, amino acids ionize. The concentration of protons at this pH causes the amino group to act as a base, and it attracts a proton to form NH3+. The carboxyl group, in contrast, acts as an acid. The two highly electronegative oxygen atoms in this group pull the electron away from its hydrogen atom, which means that it is relatively easy for this group to lose a proton to form COO-

Hydrophobic

Nonpolar R-groups lack charged or highly electronegative atoms capable of forming hydrogen bonds with water. These R-groups are... Meaning that they do not interact with water

van der Waals interactions

Once hydrophobic side chains are close to one another, their association is further sta- bilized by electrical attractions known as van der Waals interactions. These weak attractions occur because the constant motion of electrons gives molecules a tiny asym- metry in charge that changes with time. If nonpolar mol- ecules get extremely close to each other, the minute partial charge on one molecule induces an opposite partial charge in the nearby molecule and causes an attraction. Although the interaction is very weak relative to covalent bonds or even hydrogen bonds, a large number of van der Waals interac- tions can significantly increase the stability of the structure.

The 20 Major Amino Acids Found in Organisms

each bend in a ring is the site of a carbon atom. the hydrogen atoms in these structures are also not shown. a double line inside a ring indicates a double bond.

molecular chaperone

facilitate protein folding by recognizing unfolded proteins by binding to hydrophobic patches that are not normally exposed when the proteins are folded properly. This interaction prevents the unfolded proteins from clumping together, allowing them to fold into the shape specified by their primary sequence.

10. Make a concept map (see BioSkills 12) that relates the four levels of protein structure and shows how they can contribute to the formation of hemoglobin. Your map should include the following boxed terms: Primary structure, Secondary structure, Tertiary structure, Quaternary structure, Active site, Amino acid sequence, R-groups, α-Helices.

figure A3.2

Spontaneous reaction in folding

folding does tend to be spontaneous because the chemical bonds and inter- actions that occur release enough energy to overcome this decrease in entropy and will also increase entropy in the surrounding envi- ronment. As a result, the folded molecule has less potential energy and is thus more stable than the unfolded molecule.

Secondary structures of proteins an 𝛂-helix (alpha-helix), in which the polypeptide's back- bone is coiled a 𝛃-pleated sheet (beta-pleated sheet), in which segments of a peptide chain bend 180° and then fold in the same plane

is created in part by interactions between functional groups in the peptide-bonded backbone. Secondary structures are distinctively shaped sections that are stabilized largely by hydrogen bonding that occurs between the oxygen on the C=O group of one amino acid residue and the hydrogen on the N-H groups of another

Glycine, Gly, (G)

nonpolar

prions

protein- aceous infectious particles.

Ribbon diagram

ribbon diagrams represent secondary structures using coils for helices and parallel arrows for pleated sheets.

Protein Structure Determines Function

ribonuclease is functional when properly folded via hydrogen and disulfide bonds. (right) When the disulfide and various noncovalent bonds are broken, ribonuclease is no longer able to function. the double arrow indicates that in this case, the process is reversible.

active site

the location where substrates bind and react became known as the enzyme's

primary structure

unique sequence of amino acids in a protein

quaternary structure

when multiple polypeptides interact to form a single protein. Stabilized by Bonds and other interactions between R-groups, and between peptide backbones of different polypeptides

Aspartate, Asp, (D)

Polar acidic, negative charge side chain

Glutamate, Glu, (E)

Polar acidic, negative charge side chain

Tyrosine, Tyr, (Y)

Polar aromatic, partial hydrophilic

Arginine, Arg, (R)

Polar, basic, positive charge

Serine, Ser, (S)

Polar, partial charges can form hydrogen bonds, Acidic

Lysine, Lys, (K)

Polar, positively charged, basic

Glutamine, Gln, (Q)

Polar, uncharged R groups

polypeptides

Polymers that contain 50 or more amino acids are called

R-group orientation

Side chains can interact with each other and with water

15. PROCESS OF SCIENCE AN-PEP was tested for its ability to digest gluten peptides in a system that mimics the human stomach. White bread was loaded into the artificial stomach with or without AN-PEP. The following graph shows the experiment results. Interpret the effect of AN-PEP on the accumulation of proline-rich gluten peptides. Explain why the peptide concentration increases in the negative control.

The AN-PEP system has fewer proline-rich peptides in comparison to the negative control. The increase in peptide concentration in the negative control may result from the digestion of gluten by the normal gut enzymes, which would release more of the proline- rich peptide being evaluated

9. Based on what you know of the peptide bonds that link together amino acid residues, why would proline's side chain reduce the flexibility of the backbone?

The side chain of proline is covalently bonded to the nitrogen in the core amino group as well as to the central carbon. This would restrict the movement of the side chain relative to the core nitrogen and would further restrict the backbone when the nitrogen par- ticipated in a peptide bond with a neighboring amino acid

12. When you eat gluten, enzymes present in your stomach and intestines digest all but a few short peptides. How do enzymes accomplish this activity? a. The active site of an enzyme binds to a gluten protein and facilitates the hydrolysis reaction that breaks apart peptide bonds. b. An enzyme binds to the active site of a gluten protein and speeds up the condensation reaction that breaks apart peptide bonds. c. The active site of an enzyme binds to a gluten protein and reacts with it to break apart hydrogen bonds. d. An enzyme binds to the active site of a gluten protein and catalyzes the reactions that break apart hydrogen bonds.

a.

4. What is an active site? a. the location in an enzyme where substrates bind and react b. the place where a molecule or ion binds to an inactive protein to induce a shape change c. the portion of a motor protein involved in moving cargo in a cell d. the site on an antibody where it binds to bacterial cells or viruses

a.

protein

any chain of amino acid residues

Disulfide bonds

are frequently referred to as bridges, because they create strong links between distinct regions of the same polypeptide or two separate polypeptides.

2. What type of bond is directly involved in the formation of an α-helix? a. peptide bonds between amino acid residues b. hydrogen bonds between amino acid residues c. van der Waals interactions between nonpolar residues d. disulfide bonds that form between cysteine residues

b.

hydrolysis

breaks polymers apart by adding a water molecule

amino acids

building blocks of proteins

11. The typical college student diet is rich in gluten-containing foods. Make a list of six items that you would not be able to eat if you were diagnosed with celiac disease.

burrito, pizza, bagels, cereal, battered fish, pretzels

7. Why are proteins not considered to be a good candidate for the first living molecule? a. Their catalytic capability is not sufficient for most biological reactions. b. Their amino acid monomers were not likely present in the prebiotic soup. c. They cannot serve as a template for replication. d. They could not have polymerized from amino acid monomers under early Earth conditions.

c.

denatured

could be unfolded ex. rna treated with compounds that break hydrogen bonds and disulfide bonds. The denatured ribonuclease was unable to function normally—it could no longer break apart nucleic acids.

1. What two functional groups are bound to the central carbon of every free amino acid monomer? a. an R-group and a hydroxyl group b. an N-H group and a carbonyl group c. an amino group and a hydroxyl group d. an amino group and a carboxyl group

d.

Flexibility

Although the peptide bond itself cannot rotate because of its double-bond nature, the single bonds on either side of the peptide bond can rotate. As a result, the structure as a whole is flexible

14. Recall that proline often introduces kinks in the backbone of a polypeptide. These kinks make it difficult for enzymes in your gut to fully digest gluten. In people with celiac disease, certain proline-rich peptides left over after gluten digestion will trigger an abnormal immune response. Researchers have identified a mold enzyme called AN-PEP that effectively digests proline-rich peptides. Predict where the structural differences would occur between AN-PEP and other enzymes that do not digest the peptides.

Amino acid differences would be expected in the active site or in regions that affect the folded structure of this site. Either of these changes could result in a different active site that is better at either binding to the peptides or catalyzing the reaction to cleave the peptide bonds.

substrates

Catalyzed reactions involve one or more reactants, called

Changes in Primary Structure Affect Protein Function.

Compare the primary structure of normal hemoglobin (a) with that of hemoglobin molecules in people with sickle-cell disease (b). the single amino acid change causes red blood cells to change from their normal disc shape in (a) to a sickled shape in (b) when oxygen concentrations are low.

Covalent bonding

Covalent bonds can form between the side chains of two cysteines through a reaction between the sulfhydryl groups.

Five types of interactions involving R-groups are particularly important:

Hydrogen bonding, Hydrophobic interactions, wan der Waals interactions, Covalent bonding, Ionic bonding

Hydrogen bonding

Hydrogen bonds form between polar side chains and opposite partial charges either in the peptide backbone or other R-groups.

6. Explain how molecular chaperones facilitate protein folding in many different polypeptides, each with their own specific shape.

Molecular chaperones facilitate folding by preventing unfolded proteins from clumping together so that they can fold into the shapes that are determined by the information in their primary structures.

Transport

Proteins allow particular molecules to enter and exit cells or carry them throughout the body.

R-group, or side chain

R-groups vary from a single hydrogen atom to large structures containing carbon atoms linked into rings. The properties of amino acids vary because their R-groups vary.

Why is the order and type of residues in the primary structure of a protein important?

Recall that the R-groups present on each amino acid affect its chemical reactivity and solubility. It's there- fore reasonable to predict that the order of the R-groups pres- ent in a polypeptide will affect that molecule's properties and function.

peptide bond

The chemical bond that forms between the carboxyl group of one amino acid and the amino group of another amino acid or The C-N covalent bond that results from this condensation reaction explanation: When a water molecule is removed in the condensation reaction, the carboxyl group is converted to a carbonyl functional group (C=O) and the amino group becomes simply N-H in the resulting polymer.

Based on the relative electronegativities of O, n, C, S, and h (see Chapter 2), explain why the r-groups highlighted in green are nonpolar and why r-groups highlighted in pink are polar

The green R groups contain mostly C and H, which have roughly equal electronegativites. Electrons are evenly shared in C-H bonds and C-S bonds , so the groups are non polar. Cysteine has a sulfur that is slightly more electronegative than hydrogen, so it will be less non polar than the other green groups. All of the pink R-groups have a highly electronegative oxygen atom with a partial negative charge, making them polar

3. What type of information is used to direct different polypeptides to fold into different shapes?

The info present in the order and type of amino acids that make up the polypeptide(the primary structure)

5. QUANTITATIVE If a cell were to use only 10 of the 20 possible amino acids, how much of an effect would you expect this to have on protein diversity? Calculate and compare the number of different sequences that can be generated by randomly assembling either 10 or 20 amino acids into peptides that are five residues long.

The protein diversity would significantly decrease. Using 20 different amino acids, a total of 205 (3.2 : 106) different peptides can be generated. If only 10 different amino acids were available, then the num- ber of peptides would drop to 105 (1 : 105). This would be a 32-fold decrease in diversity.

Directionality

There is an amino group (-NH3+) on one end of the backbone and a carboxyl group (-COO-) on the other

dehydration/condensation reaction

These reactions are aptly named because the newly formed bond results in the loss of a water molecule

oligopeptide

When fewer than 50 amino acids are linked together in this way, the resulting polymer

13. QUANTITATIVE One of the peptides that can be recovered after gluten digestion is 33 residues long; 13 of the 33 residues are proline. How many times would you expect proline to appear in this peptide if it were made up of a completely random assortment of the 20 most common amino acids?

You would expect proline to appear once or twice in the chain (at a frequency of 1/20 at each of the 33 posi- tions, or 1.65 times).

Normal prion protein vs. infectious prion protein

a normal, noninfectious prion protein with α-helices; and (b) the infectious form with β-pleated sheets that causes mad cow disease in cattle