Chapter 18: Protein Structure and Function

are biological catalysts, and most of them are proteins Reactions that would take days or weeks or require extremely high temperatures without enzymes are completed in an instant.

enzymes

amino acids that cannot be synthesized by the body and are required in the body;

essential

a protein involved in coagulation of blood, compromises 7% of the plasma protein.

fibrinogen

IgM, IgG, IgA, IgD, IgE, make up the remaining 11% of the plasma proteins. The ____________ _______________are synthesized by B lymphocytes but most of the remaining plasma proteins are synthesized in the liver. In fact, a frequent hallmark of liver disease is reduced amounts of one or more of the plasma proteins.

gamma-globulins or antibodies

Soluble proteins are usually ____________ proteins. they have 3D structures called the tertiary structure of the protein, which are distinct from their secondary structure

globular

many of the receptor proteins on cell surfaces are

glycoproteins These are proteins with sugar groups covalently attached. Each of the subunits of hemoglobin is bound to an iron-containing heme group. The heme group is a large, unsaturated organic cyclic amine with an irone ion coordinated within it. As in the case of hemoglobin, the prosthetic group often determines the function of the prote. In hemoglobin, it is the iron-containing heme groups that have the ability to bind reversibly to oxygen.

is the oxygen storage protein of skeletal muscle.

myoglobin myoglobin has a greater attraction for oxygen than does hemoglobin, which allows efficient transfer of oxygen from the bloodstream to the cells of the body.

Amino acids are also used in the biosynthesis of a large number of important molecules called

nitrogen compounds This group includes some hormones, the heme groups of hemoglobin and myoglobin, and the nitrogen-containing bases found in DNA and RNA.

are those amino acids that can be synthesized by the body and need not be included in the diet

nonessential

serve as sources of amino acids for embryos or infants. Egg albumin and casein in milk are examples of nutrient storage proteins.

nutrient proteins

The stomach enzyme _________ begins the digestion by hydrolyzing some of the peptide bonds of the protein. This breaks the protein down into smaller peptides.

pepsin

Production of pepsin and other proteolytic digestive enzymes must be carefully controlled because the active enzymes would digest and destroy the cells that produce them. Thus pepsis is actually synthesized and secreted in an inactive form called ___________________. which has an additional 42 amino acids in its primary structure. These are removed in the stomach to produce active pepsin.

pepsinogen

is the amino acid sequence of the protein. The___________ ____________ results from the formation of covalent peptide bonds between amino acids. Peptide bonds are amide bonds formed between the carboxylate group of one amino acid and the amino group of another.

primary structure

The _____________ ____________ of a protein is the amino acid sequence of the protein chain. It results from the covalent bonding between the amino acid residues in the chain (peptide bonds)

primary structure The primary structures of proteins are translations of information contained in genes. Each protein has a different primary structure with different amino acid residues in different places along the chain. This sequence of amino acid residues is dictated by the sequence of the gene. Ultimately, it is the primary structure of a protein that will determine its biologically active form. The interactions among the R groups of the amino acids in the protein chain depend on the location of those R groups along the chain. These interactions will govern how the protein chain folds, which in turn, dictates its final 3D structure and its biological function

In some cases, quaternary structure of a functional protein involves binding to a non-protein group. This additional group is called a

prosthetic group

The L-configuration of alpha-amino acids is isolated from

proteins

are also the most abundant macromolecules in the cell and have a wide variety of biological functions

proteins

is a word derived from a Greek word that means "of first importance." __________ are a very important class of food molecules because they provide an organism not only with carbon and hydrogen, but also with nitrogen and sulfur (which are unavailable from fats and carbs)

proteins

Fibrous proteins are structural proteins arranged in fibers or sheets that have only one type of secondary structure. The alpha-keratins are fibrous proteins that form the covering (hair, wool, nails, hooves, and fur) of most land animals. Human hair provides a typical example of the structure of alpha-keratins. The proteins of hair consist almost exclusively of polypeptide chains coiled up into alpha-helices. A single alpha-helix is coiled in a bundle with two other helices to give a three-stranded superstructure called a

protofibril

For many proteins, the functional form is not composed of a single peptide but is rather an aggregate of smaller globular peptides. For instance, the protein hemoglobin is composed of four individual globular peptide subunits: two identical alpha-subunits and two identical B-subunits. Only when the four peptides are bound to one another is the protein molecule functional. The association of several polypeptides to produce a functional protein defines the

quaternary structure of a protein.

The forces that hold the quaternary structure of a protein are

the same as those that hold the tertiary structure.

what are the 9 hydrophobic amino acids?

alanine, valine, leucine, isoleucine, proline, glycine, methionine, phenylalanine, and tryptophan. The R group of proline is unique; it is actually bonded to the alpha-amino group, forming a secondary amine.

The most abundant protein in the blood is ___________, making up about 55% of the blood protein.

albumin Albumin contributes to the osmotic pressure of the blood simply because it is a dissolved molecule. It also serves as a nonspecific transport molecule for important metabolites that are otherwise poorly soluble in water. Among the molecules transported through the blood by albumin are bilirubin (a waste product of the breakdown of Hgb), Ca2+, and fatty acids (organic anions).

prtofibrils are part of an array known as a

microfibril these structures, which resemble "molecular pigtails" possess great mechanical strength, and they are virtually insoluble in water.

are necessary for all forms of movement. Our muscles, including that most important muscle, the heart, contract and expand through the interaction of actin and myosin proteins. Sperm can swim because they have long flagella made up of proteins.

movement proteins

The hydrophilic side chains are often found on the surfaces of proteins. The polar amino acids can be subdivided into three classes, which are?

1. Polar, neutral amino acids 2. Negatively charged amino acids 3. Positively charged amino acids.

have R groups that have a high affinity for water but are not ionic at pH 7. Serine, threonine, tyrosine, cysteine, asparagine, and glutamine fall into this category. Most of these amino acids associate with one another by hydrogen bonding, but cysteine molecules form disulfide bonds with one another.

1. Polar, neutral amino acids

have ionized carboxyl groups in their side chains. At pH 7, these amino acids have a net charge of -1. Aspartate and glutamate are the two amino acids in this category. They are acidic amino acids because ionization of the carboxylic acid release a proton.

2. Negatively charged amino acids

The names of the amino acids can be abbreviated by a?

3-letter code and by a 1-letter code:

At pH 7, lysine arginine, and hisitinde have a net positive charge because their side chains contain positive groups. These amino groups are basic because the side chain reacts with water, picking up a proton and releasing a hydroxide anion.

3. Positively charged amino acids.

The blood plasma of a healthy individual typically contains

60-80g/L of protein

Explain O2 transport from mother to fetus

A fetus receives o2 from its mother by simple diffusion across the placenta. If both the fetus and the mother had the same type of Hgb, this transfer process would not be efficient because the Hgb of the fetus and the mother would have the same affinity for O2. The fetus, however, has a unique type of Hgb, called fetal Hgb. This unique hemoglobin molecule has a greater affinity for oxygen than does the mother's Hgb. oxygen is therefore efficiently transported via the circulatory system from the lungs of the mother to the fetus. The biosynthesis of fetal hemoglobin stops shortly after birth when the genes encoding fetal Hgb are switched off and the genes coding for adult hemoglobin are turned on.

what is the relationship between sickle cell trait and malaria?

A relationship exists between sickle cell trait and resistance to malaria. In some parts of Africa, up to 20% of the population has sickle cell trait, in those same parts one of the leading causes of death is malaria. The presence of sickle cell trait is linked to an increased resistance to malaria because the malarial parasite cannot feed efficiently on sickle RBCs. People who have sickle cell disease die young, those without sickle cell trait have a high probability of succumbing to malaria. People who have sickle cell trait do not suffer much from sickle cell anemia and simultaneously resist deadly malaria. Because those with sickle cell trait have a greater chance of survival and reproduction, the sickle cell hgb is maintained in the population.

is another inhibitor found in the bloodstream. This protein, along with amyloid proteins, is found in the amyloid plaques characteristics of Alzheimers.

Alpha1-antichymotrypsin As a result, it has been suggested that an overproduction of the protein may contribute to it. In the blood, it is also found complexed to prostate specific antigen (PSA), the protein antigen that is measured as an indicator of prostate cancer. Elevated PSA levels are observed in those with the disease. It is interesting to note that PSA is a chymotrypsin-line proteolytic enzyme.

represent 13% of the blood plasma proteins and include transferrin (an iron transport protein) and LDL.

B-globulins

The second common secondary structure in proteins resembles the pleated folds of drapery. All of the carbonyl oxygens and amide hydrogens in a _________ _______________are involved in hydrogen bonds, and the polypeptide chain is nearly completely extended.

B-pleated sheet The polypeptide chains in a B-pleated sheet can have two orientations. If the N-termini are head to head the structure is known as a parallel B-pleated sheet. If the N-terminus of one chain is aligned with the C-terminus of a second chain (head to tail), the structure is known as an antiparallel B-pleated sheet.

How does pH effect proteins?

Because of the R groups of amino acids, all proteins have a characteristic electric charge. Because every protein has a different amino acid composition, each will have a characteristic net electric charge on its surface. The positively and negatively charged R groups on the surface of the molecule interact with ions and water molecules, adn these interactions keep the protein in solution with the cytoplasm. When the pH is changed dramatically, teh acid or base will change the charge of the protein, interfering with salt bridges and hydrogen bonds that stabilize the tertiary structure. When milk sits in the fridge, bacteria begins to grow, they use the milk sugar lactose as energy in the process of fermentation and produce lactic acid as a by-product. The additional acid results in the protonation of exposed carboxylate groups on the surface of dissolved milk proteins. As a result, they lose their characteristic surface charge and can no longer be associated with ions and water or repel one another. Then the proteins tend to clump together and precipitate out of solution (forming curds).

How does temperature effect proteins?

Consider the effect of increasing temperature on a solution of proteins-for instance, egg white. At first, increasing the temperature simply increases the rate of molecular movement, the movement of the individual molecules within the solution. Then, as the temperature continues to increase, the bonds within the proteins begin to vibrate more violently. Eventually, the weak interactions, like hydrogen bonds and hydrophobic interactions, that maintain the protein structure are disrupted. The protein molecules are denatured as they lose their characteristic 3D conformation and become completely disorganized. Coagulation occurs as the protein molecules then unfold and become entangled. At this point they are no longer in solution; they have aggregated to become a solid and will precipitate out of the solution. The egg white began as a viscous solution of egg albumins; but when it was cooked, the proteins were denatured and coagulated to become solid Many of the proteins of our cells, like enzymes, are in the same kind of viscous solution within the cytoplasms. To continue to function properly, they must remain in solution and maintain the correct 3D configuration. If the body temperature becomes too high, or if local regions of the body are subjected to very high temperatures, as when you touch a hot cookie sheet, cellular proteins become denatured. They lose their function, and the cell or organism dies.

How do detergents interact with proteins?

Detergents have both a hydrophobic region (fatty acid tail) and a polar/hydrophilic region when detergents interact with proteins, they disrupt hydrophobic interactions, causing the protein chain to unfold.

what causes denaturation of proteins

Extremes of pH or temperature have a drastic effect on protein conformation, causing the molecule to lose their characteristic 3D shape. Denaturation occurs when the organized structures of a globular protein, the alpha-helix, the B-pleated sheet, and tertiary folds become completely disorganized. However, it does not alter the primary structure. Denaturation of an alpha helical protein is shown:

How do heavy metals interact with proteins?

Heavy metals like mercury or lead may form bonds with negatively charged side chain groups. This interferes with the salt bridges formed between amino acid R groups of the protein chain, resulting in a loss of conformation. Heavy metals may also bind to sulfhydryl groups of a protein. This may cause a profound change in the 3D structure of the protein, accompanied by loss of function.

Almost all alpha-amino acids isolated from proteins in nature are members of the

L-family. In other words, the orientation of the four groups around the chiral carbon of these alpha-amino acids resembles the orientation of the four groups around hte chiral carbon of the L-glyceraldehyde.

what affect do organic solvents have on proteins?

Polar organic solvents like rubbing alcohol, denature proteins by disrupting hydrogen bonds within the protein, in addition to forming hydrogen bonds with the solvent (water). The nonpolar regions of these solvents interfere with hydrophobic interactions in the interior of the protein molecule, thereby disrupting the conformation. Traditionally a 70% solution of rubbing alcohol is as a disinfectant or antiseptic, but now research shows its not effective.

what happens as protein digestion continues into the small intestine?

Protein digestion continues in the SI where the enzymes trypsin, chymotrypsin, elastase and others catalyze the hydrolysis of peptide bonds at different sites in the protein. For instance, chymotrypsin cleaves peptide bonds on the carbonyl side of aromatic amino acids and trypsin cleaves peptide bonds on the carbonyl side of basic amino acids. Together these proteolytic enzymes degrade large dietary proteins into amino acids that can be absorbed by cells of the SI.

what is a peptide bond?

Proteins are linear polymers of L-alpha amino acids in which the carboxyl group of one amino acid is linked to the amino group of another amino acid. The peptide bond is an amide bond formed between the -COO- group of one amino acid and the alpha -N+H3 group of another amino acid. The reaction, below for the amino acids glycine and alanine, is a condensation reaction, because a water molecule is lost as the amide bond is formed

is concerned with the topological, spatial arrangements of two or more peptide chains with respect to each other. How is one chain oriented with respect to another? What is the overall shape of the final functional protein?

Quaternary structure

is a human genetic disease that first appeared in west and central africa. It afflicts about 0.4% of African americans. These individuals produce a mutant hgb known as sickle cell hemoglobin (Hb S). sickle cell anemia receives its name from the sickled appearance of the RBCs that form in this condition. The sickle cells are unable to pass through the small capillaries of the circulatory system, and circulation is hindered. This results in damage to many organs especially bones, kidneys and can lead to early death.

SICKLE CELL ANEMIA Sickle cell hemoglobin differs from normal Hgb by a single amino acid. In the B-chain of sickle cell hgb, a valine (hydrophobic amino acid) has replaced a glutamic acid (negatively charged amino acid). This substition provides a basis for the binding of hemoglobin S molecules to one another. When oxyhemoglobin S unloads its o2, individual deoxyhemoglobin S molecules bind to one another as long polymeric fibers. This occurs because the valine fits into a hydrophobic pocket on the surface of a second deoxyhemoglobin S molecule. The fibers generated in this way radically alter the shape of the RBC, resulting in the sickling effect. Sickle cell anemia occurs in individuals who have inherited the gene for sickle cell hemoglobin from both parents. Afflicted individuals produce 90-100% defective B-chains. Individual who inherit one normal gene and one defective gene, a condition known as sickle cell trait., produce both normal and altered B-chans. Although not severely affected, they have a 50% chance of passing it to their children.

How does mechanical stress affect proteins?

Stirring, whipping or shaking can disrupt the weak interactions that maintain protein confirmation. The drag of the whisk or beater creates a pulling force that unfolds and stretches the proteins.

How is L vs D decided in amino acids

The D-L notation is very similar to that discussed for carbohydrates, but instead of the -OH group we use the -N+H3 group to determine which is D and which is L. Below, notice that the most oxidized end of the molecule, the carbonyl group of glyceraldehyde or carboxyl group of alanine, is drawn at the top of the molecule. In the D-isomer of glyceraldehyde, the -OH group is on the right. And likewise the -N+H3 is on the right in alanine.

what is the importance of the R group of an amino acid

The alpha carbon of each amino acid is also bonded to a hydrogen atom and a side chain, or R group. In a protein, the R groups interact with one another through a variety of weak attractive forces. These interactions participate in folding the protein chain into a precise 3D shape that determines its ultimate function. They also serve to maintain that 3D conformation.

what is different about the amino acid glycine

The alpha-carbon is attached to four different groups in all amino acids except glycine. The alpha carbon of most alpha amino acids is therefore chiral, allowing mirror image forms, enantiomers, to exist. Glycine has two hydrogen atoms attached to the alpha-carbon and is the only amino acid commonly found in proteins that is not chiral.

How is tertiary structure maintained?

The globular tertiary structure forms spontaneously and is maintained as a result of interactions among the side chains, the R groups, of the amino acids. The structure is maintained by the following molecular interactions: Van der waals forces (LD forces and D-D attractions) between the hydrophobic R groups Hydrogen bonds between the polar R groups Ionic bonds (salt bridges) between the oppositely charged R groups Covalent bonds between the thiol-containing amino acid residues. Two of the polar cysteines can be oxidized to a dimeric amino acid called cystine The importance of these bonds becomes clear when we realize that it is the tertiary structure of the protein that defines its biological function. Most of the time, nonpolar side chains of amino acid residues are buried, out of contact with water. Polar and charged side chain amino acid residues lie on the surfaces of globular proteins. Globular proteins are extremely compact. The tertiary structure can contain regions of alpha-helix and regions of B-pleated sheets. "Hinge" regions of a random coil connect regions of alpha-helix and Beta-pleated sheet. Because of its cyclic structure, proline disrupts an alpha-helix. As a result, proline is often found in these hinge regions.

what is the major structural property of alpha helices?

The major structural property of a coiled coil superstructure of alpha-helices is its great mechanical strength. This property is applied very efficiently in both the fibrous proteins of skin and those of muscle.

what indicates the number of amino acids in small peptides?

The number of amino acids in small peptides is indicated by the prefixes di-(two units), tri, tetra and so on. Peptides are named as derivatives of the C-terminal amino acid, which receives its entire name. For all other amino acids, the ending -ine is changed to -yl.

how does O2 transfer from lungs to tissues

The oxygenation of hemoglobin in the lungs and the transfer of oxygen from hemoglobin to myoglobin in the tissues are very complex processes. The oxygenation of hemoglobin in the lungs is greatly favored by the difference in the oxygen partial pressure (pO2) in the lungs and in the blood. The pO2 in the air in the lungs is approximately 100 mmHg, and the pO2 in the oxygen-depleted blood is only about 40mmHg. Oxygen diffuses from the region of high pO2 in the lungs to the region of low pO2 in the blood. There it enters RBCs and binds to Fe2+ ions of the heme groups of deoxyhemoglobin, forming oxyhemoglobin. This binding actually helps bring more O2 into the blood.

How is quaternary structure maintained?

The quaternary structure is maintained by the same forces that are responsible for tertiary. It is the tertiary and quaternary structures of proteins that ultimately define its function.s ome have a fibrous structure with a great mechanical strength. These make up the major structural components of the cell and the organism. Often they are also responsible for the movement of the organism. Others fold into globular shapes. Most of the transport proteins, regulatory proteins, and enzymes are globular proteins. The very precise 3D structure of each of these proteins allows each to carry out its specific function in the body.

The repeat distance of the helix, or its pitch, is _____angstroms, and there are _____ amino acids per turn of the helix

The repeat distance of the helix, or its pitch, is 5.4 angstroms, and there are 3.6 amino acids per turn of the helix

The most common type of secondary structure is a coiled, helical conformation

alpha helix Every amide hydrogen and carbonyl oxygen associated with the peptide backbone is involved in a hydrogen bond when the chain coils into an alpha helix. These hydrogen bonds lock the alpha-helix into place Every carbonyl oxygen is hydrogen-bonded to an amide hydrogen four amino acids away in the chain The hydrogen bonds of the alpha-helix are parallel to the long axis of the helix The polypeptide chain in an alpha-helix is right-handed. It is oriented like a normal screw. Turn clockwise, it goes into the wall, counterclockwise it comes out of the wall.

Structure of Amino Acids The proteins of the body are made up of some combination of twenty different subunits called

alpha-amino acids

alpha 1 and alpha 2) make up 13% of the plasma proteins. They include glycoproteins (proteins with sugar groups attached), HDL, haptoglobin (a transport protein for free hemoglobin), ceruloplasmin (a copper transport protein), a prothrombin (a protein involved in blood clotting), and VLDL.

alpha-globulin The most abundant alpha1 globulin is alpha1-antitrypsin. Although the name leads us to believe that this protein inhibits a digestive enzyme trypsin, the primary function of it is the inactivation of an enzyme that causes damage to the lungs.

Protein derived from animal sources is generally _________________ protein, that is it provides all of the essential and nonessential amino acids in approximately correct amounts for biosynthesis

complete

include antibodies (or immunoglobulins) which are specific protein molecules produced by specialized cells of the immune system in response to foreign antigens. These foreign invaders include bacteria and viruses that infect the body.

defense proteins

The molecule formed by condensing two amino acids is called a

dipeptide

what is the N-terminal amino acid vs C-terminal

he amino acid with a free alpha -N+H3 is known as the amino terminal, or simply the N-terminal amino acid reside or N-terminus, and the amino acid with a free COO- group is known as the carboxyl, or C-terminal amino acid residue or C-terminus. Structures of proteins are conventionally written with their N-terminal amino acid on the left

To overcome this solubility problem, we have an oxygen transport protein is found in RBCs and is the oxygen transport protein of higher animals

hemoglobin

is a tetramer composed of four polypeptide subunits: two alpha subunits and two B-subunits. Because each subunit contains a heme group, a ___________ molecule can bind four molecules of oxygen.

hemoglobin

The forces that maintain the secondary structure of a protein are?

hydrogen bonds between the amide hydrogen and the carbonyl oxygen of the peptide bond

The side chains of the remaining amino acids are polar. Because they are attracted to polar water molecules, they are said to be

hydrophillic amino acids

The side chains of some amino acids are nonpolar. They prefer contact with one another over contact with water and are said to be

hydrophobic amino acids.

proteins derived from vegetable sources are generally ___________________ proteins because they lack a sufficient amount of one or more essential amino acids. Only a few vegetable source provide complete protein: soy, quinoa, buckwheat

incomplete

Most fibrous proteins, such as silk, collagen, and the alpha-keratins are almost completely __________ in water.

insoluble

control many aspects of cell function, including metabolism and reproduction. We can function only within a limited set of conditions. For lift to exist, body temperature, the pH of the blood, and blood glucose levels must be carefully regulated. Many of the hormones that regulate body function, such as insulin and glucagon, are proteins.

regulatory proteins

Nineteen of the twenty amino acids that are commonly isolated from proteins have this same general structure; they are primary amines on the alpha carbon. The remaining amino acid, proline, is a

secondary amine

as the protein chain grows, numerous opportunities for noncovalent interactions in the backbone of the polypeptide chain becomes available. These cause regions of the chain to fold and orient themselves in a variety of conformational arrangements. The secondary level of structures includes the alpha-helix and the B-pleated sheet, which are the result of hydrogen bonding between the amide hydrogens and carbonyl oxygens of the peptide bonds. Different regions of the chain may be involved in different types of __________ structure arrangements; some regions might be alpha-helix and others might be a B-pleated sheet.

secondary structure

Regions of the primary sequence of a protein, the chain of covalently linked amino acids, fold into regularly repeating structures that resemble designs in a tapestry. These repeating structures define the _____________- _____________of the protein

secondary structure The secondary structure is the result of hydrogen bonding between the amide hydrogens and carbonyl oxygens of the peptide bonds. Many hydrogen bonds are needed to maintain the secondary structure and thereby the overall structure of the protein. Different regions of a protein chain may have different types of secondary structure. Some regions of a protein chain may have a random or non regular structure, however, the two most common types of secondary structure are the alpha-helix and the Beta-pleated sheet because they maximize hydrogen bonding in the backbone.

The majority of cellular proteins are ____________ in cell cytoplasm

soluble

Digestion of dietary protein begins in the

stomach

provide mechanical support to large animals and provide them with their outer coverings. Our hair and fingernails are largely composed of the protein keratin. Other proteins provide mechanical strength for our bones, tendons, and skin. Without such support, large multicellular organisms like ourselves could not exist.

structural proteins

refers to the 3D shape of the entire peptide chain. The regions of secondary structure, alpha helix, and Beta pleated sheet, further fold on themselves to achieve the tertiary structure.

tertiary structure

when we discuss ___________- structure, we are interested in the overall folding of the entire chain. In other words, we are connected with the further folding of the secondary structure. Are the two ends of the chain close together or far apart? What general shape is involved? Both noncovalent interactions between the R groups of the amino acids and covalent disulfide bridges play a role in determining the tertiary structure. The noncovalent interactions include hydrogen bonding, ionic bonding, and van der waals forces (LD forces and D-D attractions).

tertiary structure

carry materials from one place to another in the body. The protein transferrin transports iron from the liver to the bone marrow, where it is used to synthesize the heme group for hemoglobin. The proteins hemoglobin and myoglobin are responsible for transport and storage of oxygen in higher organisms, respectively.

transport proteins

. Any neutral molecule with equal numbers of positive and negative charges is called a

zwitterion Thus, amino acids in water exist as dipolar ions called zwitterions.