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6 Protein Structure: An Overview and Primary Protein Structure (1°)

6 Protein Structure: An Overview and Primary Protein Structure (1°)

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Protein structure: An Overview and Primary Protein structure 11°2



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The primary protein structure 11°2 of a protein is the sequence in which its amino

acids are lined up and connected by peptide bonds. Along the backbone of the protein

is a chain of alternating peptide bonds and a@carbon atoms. The amino acid side chains

(R1, R 2) are substituents along the backbone, where they are bonded to the a@carbon

atoms. Note the positions of the hydrogen atoms bonded to the amino nitrogen atom,

the R groups, and the carbonyl oxygen atom. These specific orientations contribute to

secondary structure, which is discussed in the next section of this chapter.

SECTION 18.6



Peptide bond



+

H3N



R1



O



C



C



H



R2



O



N



C



C



H



H



601



Primary protein structure The

sequence in which amino acids are

linked by peptide bonds in a protein.



Side chains



R3



O



N



C



C



H



H



R4



O



N



C



C



H



H



Protein backbone

Review the properties of carbon—

The carbon and nitrogen atoms along the backbone lie in a zigzag arrangement, with

oxygen double bonds in Section 13.4.

tetrahedral bonding around the a@carbon atoms. The free electron pair on each N-atom is

shared with the adjacent C “ O bond. This electron sharing is called delocalization, which

you saw in the benzene molecule in Section 13.8. Sharing

electrons from the N-atom makes the C ¬ N bond similar Planar units along a protein chain

to a double bond in that there is no rotation around it. The

H

H

H R

H R

H

O

O

result is that the carbonyl group, the ¬ NH group bonded

to it, and the two adjacent a@carbons form a rigid, plaN

N





C

C

N

nar unit, as shown in the margin. The side-chain groups

C

C





C

N

N

α

on the two a@carbons extend out to opposite sides of the

plane. A long polymer chain forms a connected series of

O

O

H

H

R H

R H

R H

these planar peptide units, and the backbone NCC repeat

is a zigzag form.

The primary structure of a protein consists of the

One planar unit

amino acids being lined up one by one to form peptide

bonds in precisely the correct order for a specific protein.

The number of arrangements for a set of amino acids can

be calculated. If you have n amino acids, where n is an

integer, then the number of arrangements are n factorial, represented as n! mathematically. For example, if n = 3, then n! = 3! and 3! = 3 * 2 * 1 = 6. Therefore, there

are six ways in which three different amino acids can be joined, more than 40,000 ways in

which eight amino acids can be joined, and more than 360,000 ways in which 10 amino

acids can be joined. However, the equation predicts the total number of combinations

only if each amino acid is represented once. Despite the rapid increase in possible combinations as the number of amino acid residues present increases, the function of a protein

depends on the precise order of amino acids, and only the correct peptide can do the job.

For example, human angiotensin II must have its eight amino acids arranged in exactly

the correct order.



N-terminal end



C-terminal end



O



O

+



H3N



CH



C



NH



CH



C



O

NH



CH



CH2



CH2

COO–



CH2



C



CH

H3C



O

NH



CH

CH2



CH3



CH



C



NH



CHCH3



CH3



NH



Asp (D)



NH



O



O

CH



C



CH2



CH2



CH2



+



C



O



NH

+



N



CH2



CH2



CH2



C



O

NH



CH

CH2



CH2



N



OH



C



NH2

H2N

Arg (R)



Val (V)



Tyr (Y)



Ile (I)



His (H)



Pro (P)



Phe (F)



CO–



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CHAPTER 18



Amino Acids and Proteins



CHEMiStry in ACtion

What Is Sickle-Cell Anemia?

sickle-cell anemia is a hereditary disease caused by a genetic

difference that replaces one amino acid (glutamate, Glu) with

another (valine, Val) in each of two polypeptide chains of the

hemoglobin molecule resulting in a modified hemoglobin molecule. Affected red blood cells distort into a curved, sicklelike shape giving the disease its name. the change replaces

a hydrophilic, carboxylic acid–containing side chain (Glu) in

normal hemoglobin with a hydrophobic, neutral hydrocarbon

side chain (Val) altering the shape of the hemoglobin molecule. (the effect of this change on the charge of hemoglobin is illustrated in the Chemistry in Action “Protein Analysis

by electrophoresis,” p. 596.) instead of hemoglobin retaining

the normal soluble (globular) form both while carrying and

after releasing oxygen, it forms fibrous chains after releasing

oxygen due to the ability of modified hemoglobin molecules to

associate in a “hooked” fashion as a result of the amino acid

change in the primary structure. these associations of hemoglobin molecules in stiff, fibrous chains deform the red blood

cells, causing the disease symptoms.

sickled red blood cells are fragile and inflexible, blocking

capillaries, causing inflammation and pain, and possibly restricting blood flow in a manner that damages major organs.

Also, they have a shorter lifespan than normal red blood cells,

causing afflicted individuals to become severely anemic.

sickle-cell anemia arises by inheriting two defective copies of the hemoglobin gene, one from each parent. if a person

has one functional gene and one defective gene, he or she is

said to carry the sickle-cell trait but does not have sickle-cell

anemia. the percentage of individuals carrying the genetic

trait for sickle-cell anemia is highest among ethnic groups



More than any other kind of

biomolecule, proteins are in control of

our biochemistry. Are you wondering

how each of our thousands of proteins is

produced with all their amino acids lined

up in the correct order? The information necessary to do this is stored in

deoxyribonucleic acid (DNA), and the

remarkable machinery that does the

job resides in the nuclei of our cells.

Chapter 26 provides the details of how

protein synthesis is accomplished. In order to synthesize proteins, our cells need

a constant supply of amino acid building

blocks from the diet because human cells

can synthesize only some of the

20 amino acids used to make proteins.

Read more about diet and protein

requirements in the Chemistry in Action

“Proteins in the Diet,” page 600.



Four normal (convex) red blood cells and one sickled red blood

cell. Because of their shape, sickled cells tend to clog blood

vessels.





originating in tropical regions where malaria is prevalent. the

ancestors of these individuals survived because malaria infections were not fatal. malaria-causing parasites enter red

blood cells and reproduce there. in a person with the sicklecell trait, the cells respond by sickling and the parasites cannot multiply. As a result, the genetic trait for sickle-cell anemia

is carried forward in the surviving population. those who

carry sickle-cell trait are generally healthy and lead normal

lives; those who have sickle-cell anemia have multiple health

problems.

CiA Problem 18.6 Describe the symptoms of sickle-cell

anemia.

CiA Problem 18.7 explain the difference between sickle-cell

anemia and sickle-cell trait.



If its amino acids are not arranged properly, this hormone will not participate as it

should in regulating blood pressure.

Sometimes one or two changes in the amino acids of a peptide change the function

of the peptide. For example, two hormones secreted by the pituitary gland differ in only

two amino acids, as seen in the following figure, and as a result have entirely different

functions in the body. Oxytocin acts on uterine smooth muscle causing contractions

during labor and on mammary gland tissue to encourage milk release. With two amino

acid changes, the peptide becomes vasopressin and participates in blood pressure control by regulating both water reabsorption in the kidney and blood vessel constriction.

S

+

H3N



Cys



Tyr



Ile



S

Gln



O

Asn



Cys



Pro



Leu



Gly



C



NH2



Oxytocin



S

+

H3N



Cys



Tyr



Phe



S

Gln



O

Asn



Cys



Vasopressin



Pro



Arg



Gly



C



NH2



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SECTION 18.7



secondary Protein structure 12°2



603



So crucial is the primary structure to function—no matter how big the protein—

that the change of only one amino acid can sometimes drastically alter a protein’s biological properties. Sickle-cell anemia is the result of a single amino acid substitution

and is discussed further in the Chemistry in Action on page 602.



ProBlEM 18.20

(a) What atoms are present in a planar unit in a protein chain?

(b) How many amino acid units do these atoms come from? Why are these units

planar?

ProBlEM 18.21

How many ways can four different amino acids be arranged in a peptide so that each

peptide is unique?

ProBlEM 18.22

Why is the exact order of amino acids (primary structure) in a protein important?



18.7 Secondary Protein Structure 12°2

Learning Objectives:



• identify the a@helix and b@sheet structures and give an example of a protein that contains primarily helix and one that contains primarily sheet secondary structure.

• Describe the specific hydrogen bonding responsible for secondary structures.

• Distinguish between fibrous and globular proteins.

Without interactions between atoms in amino acid side chains or along the backbone, protein chains would twist about randomly in body fluids like spaghetti strands in boiling water.

The essential structure–function relationship for each protein depends on the polypeptide

chain being held in its necessary shape by various interactions. As we look at the secondary,

tertiary, and quaternary structures of proteins, it will be helpful to understand the kinds of

interactions that determine the shapes of protein molecules for each level of structure.

The spatial arrangement of the polypeptide backbones of proteins determines

secondary protein structure 12°2. The secondary structure includes two kinds of repeating patterns known as the alpha-helix (α-helix) and the beta-sheet (β-sheet). In

both, hydrogen bonding between backbone atoms holds the polypeptide chain in place

and connects the carbonyl oxygen atom of one peptide unit with the amide hydrogen

atom of another peptide unit 1 ¬ C “ O # # # H ¬ N ¬ 2.



Hydrogen Bonds along the Backbone

Hydrogen bonds form when a hydrogen atom bonded to a highly

electronegative atom is attracted to another highly electronegative

atom that has an unshared electron pair. The hydrogen atoms in the

¬ NH ¬ (amide) groups and the oxygen atoms in the ¬ C “ O

(carbonyl) groups along protein backbones meet these conditions.

This type of hydrogen bonding creates both pleated sheet and

helical secondary structures. Individual hydrogen bonds are weak

forces, but the sum of many weak forces, as in the helical and sheet

structures, is large enough to stabilize the structure.



H



Secondary protein structure Regular

and repeating structural patterns

(e.g., a@helix and b@sheet) created by

hydrogen bonding between backbone

atoms in neighboring segments of

protein chains.



O



R



H



C



C



N



C



N



R



H



C



C



H



O



R



R



O



H



R



C



C



H



H



H



C



N



N



C



C



H



R



O



A@Helix

A single protein chain coiled in a spiral with a right-handed (clockwise) twist is known

as an alpha-helix 1 A@helix 2 (Figure 18.1a). The helix, which resembles a coiled spring,

is stabilized by hydrogen bonds between each backbone carbonyl oxygen atom and



Hydrogen bonds between

neighboring backbone

segments



H



Alpha-helix 1 A@helix2 Secondary

protein structure in which a protein

chain forms a right-handed coil stabilized by hydrogen bonds between peptide groups along its backbone.



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CHAPTER 18



Amino Acids and Proteins



an amide hydrogen atom four amino acid residues farther along the backbone. The

hydrogen bonds lie vertically along the helix, and the amino acid R groups extend to

the outside of the coil. Although the strength of each individual hydrogen bond is small,

the large number of bonds in the helix results in an extremely stable secondary structure. A view of the helix from the top (Figure 18.1b) clearly shows the side chains on

the amino acids oriented to the exterior of the helix.







C-terminal end



3.6 amino acid

residues per turn



Figure 18.1



Alpha-helix secondary structure.

(a) The coil is held in place by hydrogen

bonds (dotted red lines) between each carbonyl oxygen and the amide hydrogen four

amino acid residues above it. The chain

is a right-handed coil (shown separately

on the right), and the hydrogen bonds lie

parallel to the vertical axis. The protein

backbone is highlighted by a ribbon in the

model on the left. (b) Viewed from the top

into the center of the helix, the side chains

point to the exterior of the helix.



H bonds



α -Carbon

Carbonyl carbon

Hydrogen

Nitrogen

Oxygen

Side chain



N-terminal end

(a)



(b)



B@Sheet

Beta-sheet 1B@sheet 2 Secondary

protein structure in which adjacent

protein chains either in the same molecule or in different molecules are held

together by hydrogen bonds along the

backbones, forming a flat sheet-like

structure.



In the beta-sheet 1 B@sheet 2 structure, the polypeptide chains are held in place by

hydrogen bonds between pairs of peptide units along neighboring backbone segments.

The protein chains, which are extended to their full length, bend at each a@carbon so

that the sheet has a pleated contour, with the R groups extending above and below the

sheet (Figure 18.2).



ProBlEM 18.23

Examine the a@helix in Figure 18.1 and determine how many backbone C and N atoms

are included in the loop between an amide hydrogen atom and the carbonyl oxygen to

which it is hydrogen bonded.

ProBlEM 18.24

Consult the b@sheet in Figure 18.2 and (a) name the bonding responsible for the sheet

formation and (b) identify the specific atoms responsible for this bonding.



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SECTION 18.7

R group



secondary Protein structure 12°2



605



Hydrogen bond

Amino-terminal



Carboxyl-terminal



Amino-terminal



R



R



R



R



R



R



R



R



R



R

R



Carboxylterminal



R

(a)

The folding is antiparallel.





R



R

(b)



Figure 18.2



Beta-sheet secondary structure.

(a) The hydrogen bonds between neighboring protein chains. The protein chains usually lie side-by-side so that

alternating chains run from the N-terminal end to the C-terminal end and from the C-terminal end to the N-terminal end

(known as the antiparallel arrangement). (b) A pair of stacked pleated sheets illustrating how the R groups point above and

below the sheets.



Secondary Structure in Fibrous and globular Proteins

Proteins are classified in several ways, one of which is to identify them as either fibrous

proteins or globular proteins. In an example of the integration of molecular structure

and function that is central to biochemistry, fibrous and globular proteins each have

functions made possible by their distinctive structures.

Secondary structure is primarily responsible for the function of fibrous

proteins—tough, insoluble proteins in which the chains form long fibers. Wool, hair,

and fingernails are made of fibrous proteins known as a@keratins, which are composed

almost completely of a-helices. In a@keratins, pairs of a-helices are twisted together

into small fibrils that are in turn twisted into larger and larger bundles. The hardness,

flexibility, and stretchiness of the material vary with the number of disulfide bonds

present. In fingernails, for example, large numbers of disulfide bonds hold the bundles

in place.

Natural silk and spider webs are made of fibroin, another fibrous protein almost

entirely composed of stacks of b@sheet. For such close stacking, the R groups must be

relatively small (see Figure 18.6b). Fibroin contains regions of alternating glycine ( ¬ H

on the a carbon) and alanine ( ¬ CH3 on the a carbon). The sheets stack so that sides

with the smaller glycine hydrogen atoms face each other and sides with the larger alanine methyl groups face each other.

Unlike fibrous proteins, globular proteins are water-soluble proteins whose

chains are folded into compact, globe-like shapes. Their structures, which vary

widely with their functions, are not repeating structures like those of fibrous proteins.

Where the protein chain folds back on itself, sections of a@helix and b@sheet are usually present, as illustrated in Figure 18.3. The presence of hydrophilic amino acid

side chains on the outer surfaces of globular proteins accounts for their water solubility, allowing them to be soluble in both intercellular and extracellular body fluids in

order to perform their disparate functions. Furthermore, many globular proteins are

enzymes that are dissolved in the intercellular fluids inside cells. The overall shapes



Fibrous protein A tough, insoluble

protein whose protein chains form

fibers or sheets.

Globular protein A water-soluble

protein whose chain is folded in a compact shape with hydrophilic groups on

the outside.



A spider web is made from fibrous

protein. The proteins found in eggs,

milk, and cheese are examples of

globular proteins.





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CHAPTER 18



Amino Acids and Proteins



COO–

Hydrophobic interactions—

water-free pocket



Pleated sheet structure



CH2C



N



O



H



Salt bridge



CH

(CH2)4NH3



–O



HN



CH2



CH3 CH3



OH



CH2CH







CH2CH



CH3 CH3

O



C



Hydrophobic

interactions



Hydrogen bond between

side chain and peptide group

+



Helical

structure



CCH2



Hydrogen bond

between

peptide groups



H3N



H



O

+



CH3



CH3



O



CH2



CH3



CHCH2CH3



C



O



Hydrogen bond

between side chains



CH3

CH3



H



CH2



Hydrogen

bonds



S



S



CH2



Disulfide bond



Figure 18.3



Interactions that determine protein shape.

The regular pleated sheet (left) and helical structure (right) are created by hydrogen bonding between neighboring backbone atoms; the other interactions involve side-chain groups that can be nearby or quite far apart in the protein chain.



of globular proteins represent another level of structure, tertiary structure, discussed

in the next section.

Table 18.4 compares the occurrences and functions of some fibrous and globular

proteins.

table 18.4  Some Common Fibrous and Globular Proteins

Name



Occurrence and Function



Fibrous proteins (insoluble)

Keratins



Found in skin, wool, feathers, hooves, silk, and fingernails



Collagens



Found in animal hide (skin), tendons, bone, eye cornea, and other

connective tissue



Elastins



Found in blood vessels and ligaments, where ability of the tissue

to stretch is important



Myosins



Found in muscle tissue



Fibrin



Found in blood clots



globular proteins (soluble)

Insulin



Regulatory hormone for controlling glucose metabolism



Ribonuclease



Enzyme that catalyzes ribonucleic acid (RNA) hydrolysis



Immunoglobulins



Proteins involved in immune response



Hemoglobin



Protein involved in oxygen transport



Albumins



Proteins that perform many transport functions in blood;

protein in egg white



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SECTION 18.8



ProBlEM 18.25

Complete the following two sentences with either globular or fibrous:

(a) Proteins with secondary structure composed primarily of alpha-helix are

_________ proteins.

(b) Proteins with secondary structure composed primarily of beta-sheets are

_________ proteins.



tertiary Protein structure 13°2



607



KEy ConCEPt ProBlEM 18.26

Why does your skin not dissolve when you go swimming or are caught in the rain?



18.8 Tertiary Protein Structure 13°2

Learning Objectives:



• identify the four specific forces responsible for tertiary structure.

• identify what forces or bonds exist between amino acid side chains.

• Distinguish between simple and conjugated protein.



The overall three-dimensional shape that results from the folding of a single protein chain is the protein’s tertiary protein structure 13°2. In contrast to secondary

structure, which depends mainly on attraction between backbone amide peptide bonds

(C “ O to HN), resulting in hydrogen bonding, tertiary structure depends mainly on

interactions of amino acid side chains (R groups) that are far apart along the entire

backbone.

Although the bends and twists of the protein chain within a globular protein may

appear irregular and the three-dimensional structure may appear random, this is not

the case. Each protein molecule folds in a distinctive manner that is determined by its

primary and secondary structure, with the forces described next holding the tertiary

structure in place. The result is maximum stability for the native protein configuration.

A native protein has the shape that allows it to function in living systems.



Hydrogen Bonds of r groups with Each other or with Backbone Atoms

Some amino acid side chains contain atoms that can form hydrogen bonds. Side-chain

hydrogen bonds can connect different parts of a protein molecule, whether they are in

close proximity or far apart along the polypeptide chain. In the protein in Figure 18.3,

hydrogen bonds between side chains have created folds in two places. Often, hydrogenbonding side chains are present on the surface of a folded protein, where they can form

hydrogen bonds with surrounding water molecules. Recall that hydrogen bonds are

noncovalent bonds.

An example of R group hydrogen bonding between the hydrogen atom of a polar

group such as hydroxyl and the oxygen or nitrogen atom of another polar group in a different amino acid is shown in the margin.



Tertiary protein structure The

way in which an entire protein chain

is coiled and folded into its specific

three-dimensional shape.



Native protein A protein with the

shape (primary, secondary, tertiary,

and quaternary structure) in which it

exists naturally in living organisms.



CH3

C



H2N



O



H



H

Thr (T)



Where there are ionized acidic and basic side chains, the attraction between their positive and negative charges creates salt bridges. A salt bridge is a noncovalent bond; it

is an ionic bond (an attraction). For example, a basic lysine side chain and an acidic

aspartate side chain have formed a salt bridge in the middle of the protein shown in

Figure 18.3.



Hydrophilic interactions between r groups and Water

Amino acids with charged R groups will interact with water through hydrogen bonding.

The figure in the margin shows the interaction between aspartic acid and water. These

interactions are attractions not covalent bonds.



CH2



+

H3N



C

O–



(CH2)4



Asp (D)



Lys (K)

O



H



H O

CH2

Asp (D)



CH2



Asn (N)

O



ionic Attractions between r groups (Salt Bridges)



C



O



O

H



C

O–



H



H

H



O

H



O

H



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CHAPTER 18



Amino Acids and Proteins



Hydrophobic interactions between r groups



Review dispersion forces in

Section 8.2 and Van der Waals forces in

Section 9.2.



Hydrocarbon side chains are attracted to each other by the dispersion forces (primarily

Van der Waals forces) caused by a momentary uneven distribution of electrons. Although this attraction is noncovalent in nature, the result is that these groups cluster

together in the same way that oil molecules cluster on the surface of water, so

that these interactions are often referred to as hydrophobic. By clustering in this

manner, the hydrophobic groups shown in Figure 18.3 and more explicitly in the

CH2

margin create a water-free pocket in the protein chain. Although the individual

attractions are weak, their large number in proteins plays a major role in stabilizing the folded structures.

Leu (L)



CH3

CH2



CH

CH3



Phe (F)



Covalent Sulfur–Sulfur Bonds: the Disulfide Bridge

In addition to the noncovalent interactions described above, one type of covalent bond

plays a role in determining protein shape. Cysteine amino acid residues have side chains

containing thiol functional groups 1 ¬ SH2 that can react to form sulfur–sulfur bonds

1 ¬ S ¬ S ¬ 2.



Disulfide bond formation was

explored in Section 14.8.



A disulfide bond



C



O



CH



C

CH2



H + H



S



S



CH2



NH



CH



C



Oxidizing

agent



O



CH



NH



Cysteine (Cys, C)



Disulfide bond A S ¬ S bond formed

between two cysteine side chains;

can join two separate peptide chains

together or cause a loop in a single

peptide chain.



O



NH



C

CH2



S



S



CH2



O



CH

NH



Cysteine (Cys, C)



If the two cysteine residues are in different protein chains, the two separate chains become covalently linked together by the disulfide bond. If the two cysteine residues are

in the same chain, a loop is formed in the chain. Insulin provides a good example.

It consists of two polypeptide chains connected by disulfide bonds in two different

places connecting the A and B chains with two interchain bonds. Additionally, the A

chain has an intrachain loop caused by a third disulfide bond.

Structure of insulin

An intrachain disulfide bond



S



5



S



15



A-chain Gly Ile Val Glu GlnCys Cys Thr Ser Ile Cys Ser Leu Tyr Gln Leu GluAsn Tyr CysAsn

21



S



S

S



Interchain disulfide bonds



S



B-chain Phe Val Asn Gln His LeuCys Gly Ser His Leu Val Glu Ala Leu Tyr Leu Val Cys Gly Glu Arg Gly Phe Phe Tyr Thr Pro Lys Ala

5

10

15

20

30

25



Interchain disulfide

bond



Intrachain disulfide

bond



Interchain disulfide

bond



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SECTION 18.8



Insulin is representative of a class of small polypeptides (proteins) that function as

hormones, which are released when a chemical message must be carried from one place

to another (angiotensin II on p. 601 is another example of a polypeptide hormone). The

structure and function of insulin are of intense interest because of its role in glucose

metabolism and the need for supplementary insulin by individuals with diabetes. Insulin signals cells to take in glucose when blood glucose levels rise; many diabetics need

supplemental insulin because their bodies either do not produce insulin or have lost

the ability to respond to their own insulin. Diabetes and the role of insulin in glucose

metabolism are discussed further in Section 22.7. Undoubtedly because of this need,

studies of insulin have led the way in developing our ability to determine the structure

of a biomolecule and prepare it synthetically.

In a historically important accomplishment, the amino acid sequence of insulin was determined in 1951—it was the first protein for which this was done. It took

15 years before the cross-linking and complete molecular structure were determined

and a successful laboratory synthesis was carried out. With the advent of biotechnology

in the 1980s, once again insulin was first. Until then, individuals with diabetes relied on

insulin extracted from the pancreases of cows, and because of differences in three amino

acids between bovine and human insulin, allergic reactions occasionally resulted. In

1982, human insulin became the first commercial product of genetic engineering to be

licensed by the U.S. government for clinical use.

The four noncovalent interactions and disulfide covalent bonds described above

govern tertiary structure. The enzyme ribonuclease, shown here as an example in its

ribbon structure, is drawn in a style that shows the combination of a@helix and b@sheet

regions, the loops connecting them, and four disulfide bonds.



tertiary Protein structure 13°2



609



We will learn more about polypeptide hormones in Chapter 28 and

diabetes in Section 22.7.



α -Helix



β -Sheet



Connecting loop



— S — S — bonds



Ribonuclease



The structure of ribonuclease is representative of the tertiary structure of globular, water-soluble proteins. The hydrophobic, nonpolar side chains congregate in a

hydrocarbon-like interior, and the hydrophilic side chains, which provide water solubility, congregate on the outside. Ribonuclease is classified as a simple protein because it is composed only of amino acid residues (124 of them). The drawing shows

ribonuclease in a style that clearly represents the combination of primary and secondary structures in the overall tertiary structure of a globular protein. The symbols in

the left side of the figure above are standard representations for these components of

protein structure.



Simple protein A protein composed

of only amino acid residues.



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Amino Acids and Proteins



Myoglobin is an example of a small globular protein, consisting of a single

amino acid chain. A relative of hemoglobin, myoglobin stores oxygen in skeletal

muscles for use when there is an immediate need for energy. Structurally, the

153 amino acid residues of myoglobin are arranged in eight a@helical segments

connected by short segments looped so that hydrophilic amino acid residues are

on the exterior of the compact, spherical tertiary structure. Like many proteins,

myoglobin is not a simple protein but is a conjugated protein—a protein that is

aided in its function by an associated non–amino acid unit. The oxygen-carrying

portion of myoglobin has a heme group embedded within the polypeptide chain.

In Figure 18.4, the myoglobin molecule is shown in two different ways; both types

of molecular representation are routinely used to illustrate the shapes of protein

molecules. Some examples of other kinds of conjugated proteins are listed in

Table 18.5.

table 18.5  Some Examples of Conjugated Proteins

(a)



(b)



Figure 18.4







Myoglobin, drawn in two styles.

In each panel, the red structure embedded in

the protein is a molecule of heme, to which

O2 binds. (a) A protein ribbon model shows

the helical portions as a ribbon. This type

of representation clearly shows protein secondary structure. (b) A computer-generated

space-filling model of myoglobin shows the

hydrophobic residues in blue and the hydrophilic residues in purple. This type of representation better conveys the overall shape and

dimensions of the protein.



Class of Protein



Nonprotein Part



Examples



Glycoproteins



Carbohydrates



Glycoproteins in cell membranes (Section 20.7)



Lipoproteins



Lipids



High- and low-density lipoproteins that transport

cholesterol and other lipids through the body (Section 24.2)



Metalloproteins



Metal ions



The enzyme cytochrome oxidase, necessary for

biological energy production, and many other enzymes



Phosphoproteins



Phosphate groups



Milk casein, which provides essential nutrients to infants



Hemoproteins



Heme



Hemoglobin (transports oxygen) and myoglobin

(stores oxygen)



Nucleoproteins



RNA



Found in cell ribosomes, where they take part in protein

synthesis



How do proteins “know” the correct three-dimensional structure to fold up

into? As a protein is synthesized, adding amino acids one at a time, from the

N-terminal end to the C-terminal end of the protein, it is anchored to a structure

called a ribosome (see Chapter 26). The lengthening protein chain folds in a manner that allows hydrophilic residues to interact with the aqueous cellular environment and sequesters the hydrophobic residues in the interior of the final structure.

This folding is encouraged by amino acid side chains that interact either with each

other or with the aqueous environment, resulting in the lowest energy state possible for the folded protein, stabilizing the structure. Many proteins spontaneously

fold into the native structure during synthesis. However, some do not. Proteins

referred to as “chaperones” guide their folding, especially if the final structure of

the protein being synthesized is unstable. The folding step for each protein must

result in a functional protein. Misfolded proteins typically are nonfunctional and

often toxic.



Conjugated protein A protein that

incorporates one or more non–amino

acid units in its structure.



Worked Example 18.4 Drawing side-Chain interactions

What type of noncovalent interaction occurs between the glutamine and threonine side chains? Draw the

structures of these amino acids to show the interaction.

AnAlySiS The side chains of glutamine and threonine contain an amide group and a hydroxyl group,



respectively. Since the hydroxyl group does not ionize, this pair will not form salt bridges. They are polar and

therefore not hydrophobic. This pair of amino acids can form a hydrogen bond between the oxygen of the

amide carbonyl group and the hydrogen of the hydroxyl group.



www.downloadslide.net

SECTION 18.8



tertiary Protein structure 13°2



Solution

The noncovalent, hydrogen bond interaction between threonine and glutamine is as follows:

C

CH



C



O

CH2



NH



CH2



C



O



NH2



H



O



CH



O



CH



CH3 NH



Worked Example 18.5 identifying Groups involved in hydrogen Bonding

Hydrogen bonds are important in stabilizing both the secondary and tertiary structures of proteins. How do

the groups that form hydrogen bonds in the secondary and tertiary structures differ?

AnAlySiS Examine the hydrogen bonding in secondary structure. See Figures 18.1 and 18.2. Note the



regularity along the backbone of the hydrogen bonding. Only hydrogen atoms on backbone nitrogen

atoms and oxygen atoms on nearby carbonyl carbon atoms are involved in this bonding. In tertiary

structure hydrogen bonding occurs primarily between polar R groups and these groups are not

necessarily nearby.



Solution

Secondary structure is the product of regular, repetitive bonding between hydrogen atoms on

backbone nitrogen atoms and oxygen atoms on nearby carbonyl carbon atoms. The regular, repetitive

bonding leads to alpha-helix and beta-pleated sheet structures.

Tertiary structure depends on several different types of bonding and not totally on hydrogen bonding. The

hydrogen bonding is primarily between R group atoms and is spread irregularly throughout the molecule.



ProBlEM 18.27

Which of the following pairs of amino acids can form hydrogen bonds between their

side-chain groups? Draw the pairs that can hydrogen bond through their side chains

and indicate the hydrogen bonds.

(a) Phe, Thr

(b) Asn, Ser

(c) Thr, Tyr

(d) Gly, Trp



KEy ConCEPt ProBlEM 18.28

Look at Table 18.3 and identify the type of noncovalent interaction expected between

the side chains of the following pairs of amino acids:

(a) Glutamine and serine

(b) Isoleucine and proline

(c) Aspartate and lysine

(d) Alanine and phenylalanine



ProBlEM 18.29

In Figure 18.3, identify the amino acids that have formed (a) hydrogen bonds from

their side chains and (b) hydrophobic side-chain interactions.

ProBlEM 18.30

For each of the conjugated proteins described, identify to which class of conjugated

protein it belongs.

(a) Cholesterol is attached to this protein in order to move through the blood system.

(b) Ionized zinc is attached to this protein so the protein can function.

(c) Phosphate groups are attached to this protein.

(d) Complex sugars are attached to this membrane protein.

(e) A large multi-ring, conjugated hydrocarbon containing a ferric ion enables this

protein to function.

(f) RNA attached to this protein facilitates protein synthesis.



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