Proteins
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Proteins (1 of 2)
Proteins serve many functions, including the following:
• 1. Structure: Collagen and keratin are the chief constituents of skin,
bone, hair, and nails.
• 2. Catalysis: Virtually all reactions in living systems are catalyzed by
proteins called enzymes.
• 3. Movement: Muscles are made up of proteins called myosin and actin.
• 4. Transport: Hemoglobin transports oxygen from the lungs to cells, other
proteins transport molecules across cell membranes.
• 5. Hormones: Many hormones are proteins, among them insulin,
oxytocin, and human growth hormone.
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Proteins (2 of 2)
• 6. Protection: Blood clotting involves the protein fibrinogen;
the body used proteins called antibodies to fight disease.
• 7. Storage: Casein in milk and ovalbumin in eggs store
nutrients for newborn infants and birds. Ferritin, a protein in the
liver, stores iron.
• 8. Regulation: Certain proteins not only control the expression
of genes, but also control when gene expression takes place.
• Proteins are divided into two types:
• Fibrous proteins
• Globular proteins
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Amino Acids
Amino acid: A compound that contains both an amino group and
a carboxyl group.
• α-Amino acid: An amino acid in which the amino group is on the carbon
adjacent to the carboxyl group.
• Although α-amino acids are commonly written in the un-ionized form, they
are more properly written in the zwitterion (internal salt) form.
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Chirality of α-Amino Acids (1 of 2)
With the exception of glycine, all protein-derived amino acids
have at least one stereocenter (the α-carbon) and are chiral.
• The vast majority of α-amino acids have the L-configuration at the
α-carbon.
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Chirality of α-Amino Acids (2 of 2)
Figure 21.2 Alanine and glyceraldehyde stereochemistry
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Protein-Derived α-Amino Acids (1 of 4)
Nonpolar side chains. Each ionizable group is shown in the
form present in highest concentration at pH 7.0).
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Protein-Derived α-Amino Acids (2 of 4)
• Polar side chains (at pH 7.0)
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Protein-Derived α-Amino Acids (3 of 4)
Acidic and basic side chains (at pH 7.0)
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Protein-Derived α-Amino Acids (4 of 4)
1. For 19 of the 20, the α-amino group is primary; for proline, it is secondary.
2. With the exception of glycine, the α-carbon of each is a stereocenter.
3. Isoleucine (left) and threonine (right) contain a second stereocenter.
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Ionization vs. pH (1 of 2)
The net charge on an amino acid depends on the pH of the
solution in which it is dissolved.
• If we dissolve an amino acid in water, it is present in the aqueous solution
as its zwitterion.
• If we add a strong acid such as HCl to bring the pH of the solution to pH
0, the strong acid donates a proton to the –COO– of the zwitterion turning
it into a positive ion.
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Ionization vs. pH (2 of 2)
• If we add a strong base such as NaOH to the solution and
bring its pH to 14, a proton is transferred from the NH3+ group
to the base turning the zwitterion into a negative ion.
• To summarize:
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Isoelectric Point (pI)
• Isoelectric point, pI:
A pH at which a sample
of amino acids or
protein has an equal
number of positive and
negative charges.
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Peptides (1 of 2)
Proteins are long chains of amino acids joined by amide bonds.
• Peptide bond (peptide linkage): The special name given to the amide
bond between the α-carboxyl group of one amino acid and the α-amino
group of another.
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Peptides (2 of 2)
• Peptide: A short polymer of amino acids joined by peptide bonds; they
are classified by the number of amino acids in the chain.
• Dipeptide: A molecule containing two amino acids joined by a peptide
bond.
• Tripeptide: A molecule containing three amino acids joined by peptide
bonds.
• Polypeptide: A macromolecule containing many amino acids joined by
peptide bonds.
• Protein: A biological macromolecule containing at least 30 to 50 amino
acids joined by peptide bonds.
• The individual amino acid units are often referred to as “residues.”
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Writing Peptides
By convention, peptides are written from the left to right,
beginning with the free –NH3+ group and ending with the
free –COO– group.
• C-terminal amino acid: The amino acid at the end of the
chain having the free –COO– group.
• N-terminal amino acid: The amino acid at the end of the
chain having the free –NH3+ group.
• Alternatively they are referred to as the C-terminus and the
N-terminus.
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Phe, Trp, and Tyr
The amino acids phenylalanine, tryptophan, and tyrosine have
aromatic rings on their side chains.
Tryptophan is the precursor to the neurotransmitter serotonin.
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Tyr and Phe
Phenylalanine and tyrosine are precursors to norepinephrine and
epinephrine, both of which are stimulatory neurotransmitters.
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Other Amino Acids
Figure 21.3
Hydroxylation
(oxidation) of proline,
lysine, and tyrosine,
respectively and
iodination for tyrosine,
give these uncommon
amino acids.
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Protein Properties (1 of 2)
Figure 21.4 A small peptide showing the direction of the
peptide chain (N-terminal to C-terminal).
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Peptide Bond
• Figure 21.5. A peptide bond is
typically written as a carbonyl
group bonded to an N–H
group. Linus Pauling,
however, discovered that
there is about 40% double
bond character to the C–N
bond and that a peptide bond
between two amino acids is
planar, which Pauling
explained using the concept
of resonance.
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Protein Properties (2 of 2)
Proteins behave as zwitterions.
Proteins have an isoelectric point, pI.
• At its isoelectric point, the protein has no net charge.
• At any pH above (more basic than) its pI, it has a net negative charge.
• At any pH below (more acidic than) its pI, it has a net positive charge.
• Hemoglobin, for example, has an almost equal number of acidic and basic
side chains; its pI is 6.8.
• Serum albumin has more acidic side chains; its pI is 4.9.
• Proteins are least soluble in water at their isoelectric points and can be
precipitated from solution when pH = pI.
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Levels of Structure
• Primary structure: The sequence of amino acids in a
polypeptide chain. Read from the N-terminal amino acid to the
C-terminal amino acid.
• Secondary structure: Conformations of amino acids in
localized regions of a polypeptide chain. Examples are
α-helix, β-pleated sheet, and random coil.
• Tertiary structure: The complete three-dimensional
arrangement of atoms of a polypeptide chain.
• Quaternary structure: The spatial relationship and interactions
between subunits in a protein that has more than one
polypeptide chain.
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Primary Structure (1 of 5)
• Primary structure: The sequence of amino acids in a
polypeptide chain.
• The number peptides possible from the 20 protein-derived
amino acids is enormous.
• There are 20 × 20 = 400 dipeptides possible.
• There are 20 × 20 × 20 = 8000 tripetides possible.
• The number of peptides possible for a chain of n amino acids
is 20n.
• For a small protein of 60 amino acids, the number of proteins
possible is 2060 ≅ 1078, which is possibly greater than the
number of atoms in the universe!
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Primary Structure (2 of 5)
Figure 21.7 The
hormone insulin
consists of two
polypeptide chains, A
and B, held together by
two disulfide bonds.
The sequence shown
here is for bovine
insulin.
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Primary Structure (3 of 5)
How important is the exact amino acid sequence?
• Human insulin consists of two polypeptide chains having a total of 51 amino
acids; the two chains are connected by two interchain disulfide bonds.
• In Table 21.2 are differences between four types of insulin.
A Chain
positions 8-9-10
B Chain
position 30
Human
-Thr-Ser-Ile
-Thr
Cow
-Ala-Ser-Val-
-Ala
Hog
-Thr-Ser-Ile-
-Ala
Sheep
-Ala-Gly-Val-
-Ala
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Primary Structure (4 of 5)
• Vasopressin and oxytocin are both nonapeptides but
have quite different biological functions.
• Vasopressin is an antidiuretic hormone.
• Oxytocin affects contractions of the uterus in childbirth
and the muscles of the breast that aid in the secretion
of milk.
• Figure 21.8 The structures of vasopressin and
oxytocin. Differences are shown in color. (next screen)
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Primary Structure (5 of 5)
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Secondary Structure
Secondary structure: Conformations of amino acids in localized
regions of a polypeptide chain.
•
The most common types of secondary structure are
α-helix and β-pleated sheet.
•
α-Helix: A type of secondary structure in which a section of polypeptide
chain coils into a spiral, most commonly a right-handed spiral.
•
β-Pleated sheet: A type of secondary structure in which two polypeptide
chains or sections of the same polypeptide chain align parallel to each
other; the chains may be parallel or antiparallel.
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Secondary Structure: The α-Helix
Figure 21.9(a) The α-Helix.
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α-Helix
In a section of α-helix
• The six atoms of each peptide bond lie in the same plane.
• The N–H groups of peptide bonds point in the same direction, roughly
parallel to the axis of the helix.
• The C=O groups of peptide bonds point in the opposite direction, also
roughly parallel to the axis of the helix.
• The C=O group of each peptide bond is hydrogen bonded to the N–H
group of the peptide bond four amino acid units away from it.
• All R– groups point outward from the helix.
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β-Pleated Sheet (1 of 2)
Figure 21.9(b) The β-pleated sheet structure.
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β-Pleated Sheet (2 of 2)
In a section of β-pleated sheet;
• The six atoms of each peptide bond of a β-pleated sheet lie in
the same plane.
• The C=O and N–H groups of the peptide bonds from adjacent
chains point toward each other and are in the same plane so
that hydrogen bonding is possible between them.
• All R– groups on any one chain alternate, first above, then
below the plane of the sheet, etc.
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Random Coil
Figure 21.10 A random coil.
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Secondary Structure (1 of 2)
• Many globular proteins contain all three kinds of
secondary structure in different parts of their
molecules: α-helix, β-pleated sheet, and random coil
(next screen).
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Secondary Structure (2 of 2)
Figure 21.11 Schematic structure of the enzyme carboxypeptidase.
The β-pleated sheet sections are shown in blue, the α-helix portions in
green, and the random coils as orange strings.
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The Collagen Triple Helix
Figure 21.12 The collagen triple helix.
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Tertiary Structure (1 of 2)
Tertiary structure: the overall conformation of an entire polypeptide
chain.
Tertiary structure is stabilized in four ways:
•
•
•
•
Covalent bonds as for example, the formation of disulfide bonds between
cysteine side chains.
Hydrogen bonding between polar groups of side chains, as for example
between the –OH groups of serine and threonine.
Salt bridges, as for example, the attraction of the –NH3+ group of lysine and
the –COO– group of aspartic acid.
Hydrophobic interactions, as for example, between the nonpolar side
chains of phenylalanine and isoleucine.
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Cysteine
The –SH (sulfhydryl) group of cysteine is easily oxidized to an
–S–S– (disulfide).
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Tertiary Structure (2 of 2)
Figure 21.14 Forces that stabilize tertiary structures of proteins.
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Quaternary Structure (1 of 4)
Quaternary structure: The arrangement of polypeptide chains
into a noncovalently bonded aggregation.
• The individual chains are held together by hydrogen bonds, salt bridges,
and hydrophobic interactions.
Hemoglobin
• Adult hemoglobin: Two alpha chains of 141 amino acids each, and two
beta chains of 146 amino acids each.
• Fetal hemoglobin: Two alpha chains and two gamma chains. Fetal
hemoglobin has a greater affinity for oxygen than does adult hemoglobin.
• Each chain surrounds an iron-containing heme unit.
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Quaternary Structure (2 of 4)
Figure 21.20 The quaternary structure of hemoglobin. The structure
of heme is shown on the next screen.
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Quaternary Structure (3 of 4)
The structure of heme.
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Quaternary Structure (4 of 4)
Integral membrane proteins form quaternary structures in
which the outer surface is largely nonpolar (hydrophobic)
and interacts with the lipid bilayer. Two of these are
shown on the next screens.
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Denaturation (1 of 2)
Denaturation: The process of destroying the native
conformation of a protein by chemical or physical means.
• Some denaturations are reversible, while others permanently
damage the protein.
Denaturing agents include:
• Heat: Heat can disrupt hydrogen bonding; in globular proteins,
it can cause unfolding of polypeptide chains with the result that
coagulation and precipitation may take place.
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Denaturation (2 of 2)
• 6 M aqueous urea: Disrupts hydrogen bonding.
• Surface-active agents: Detergents such as sodium dodecylbenzenesulfate
(SDS) disrupt hydrogen bonding.
• Reducing agents: 2-Mercaptoethanol (HOCH2CH2SH) cleaves disulfide
bonds by reducing –S–S– groups to –SH groups.
• Heavy metal ions: Transition metal ions such as Pb2+, Hg2+, and Cd2+ form
water-insoluble salts with –SH groups; Hg2+ for example forms –S–Hg–S–.
• Alcohols: 70% ethanol penetrates bacteria and kills them by coagulating
their proteins. It is used to sterilize skin before injections.
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The End
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