PEPTIDE BONDS LEVELS OF STRUCTURE

• Typically written as a carbonyl group bonded I. Primary structure: The sequence of amino
to an N-H group acids in a polypeptide chain. Read from the N-
• Linus Pauling discovered that there is about terminal amino acid to the C-terminal amino
40% double bond character to the C-N bond acid.
• Peptide bond between two amino acids is • The number peptides possible from the 20
planar, which Pauling explained using the protein-derived amino acids is enormous.
concept of Resonance • There are 20 x 20 = 400 dipeptides possible.
WRITING PEPTIDES • There are 20 x 20 x 20 = 8000 tripeptides
• By convention, peptides are written from left possible.
to right, beginning with the free -NH3+ group • The number of peptides possible for a chain of
and ending with the free -COO- group n amino acids is 20n.
• C-Terminal amino acid: amino acid at the end • For a small protein of 60 amino acids, the
of chain having free -COO- group number of proteins possible is 2060 = 1078,
• N-Terminal amino acid: the amino acid at the which is possibly greater than the number of
end of the chain having free -NH3+ group atoms in the universe!
• Alternatively, they are referred to as the C- ➔ How important is the exact amino acid
terminus and the N-terminus sequence?
• It is universal custom or rule to write o Human insulin consists of two
polypeptide chains with the N-terminal residue polypeptide chains having a total of 51
on the left because proteins are synthesized amino acids; the two chains are
from N-terminus to C-terminus connected by two interchain disulfide
bonds.
o In Table 22-2 are differences between
four types of insulin.
A Chain B Chain
positions 8-9-10 position 30
Human -Thr-Ser-Ile- -Thr
PEPTIDES AND PROTEINS Cow -Ala-Ser-Val- -Ala
Hog -Thr-Ser-Ile- -Ala
• Proteins behave as zwitterions, and proteins Sheep -Ala-Gly-Val- -Ala

have an isoelectric point, pI.

• Vasopressin and oxytocin are both
• At its isoelectric point, the protein has no net
nonapeptides but have quite different
charge.
biological functions.
• At any pH above (more basic than) its pI, it has
• Vasopressin is an antidiuretic hormone.
a net negative charge.
• Oxytocin affects contractions of the uterus in
• At any pH below (more acidic than) its pI, it has
childbirth and the muscles of the breast that
a net positive charge.
aid in the secretion of milk.
• Hemoglobin, for example, has an almost equal
• Figure 22-9 The structures of vasopressin an
number of acidic and basic side chains; its pI is
oxytocin. Differences are shown in color.
6.8.
• Serum albumin has more acidic side chains; its
II. Secondary structure: Conformations of amino
pI is 4.9.
acids in localized regions of a polypeptide
• Proteins are least soluble in water at their
chain. Examples are
isoelectric points and can be precipitated from
a-helix, b-pleated sheet, and random coil.
solution when pH = pI.
• The most common types of secondary
structure are a-helix and b-pleated sheet.
• a-Helix: A type of secondary structure in
which a section of polypeptide chain coils
into a spiral, most commonly a right-
handed spiral.

➔ In a section of a-helix
o There are 3.6 amino acids per turn of
the helix.
o The six atoms of each peptide bond lie
in the same plane.
o The N-H groups of peptide bonds point
in the same direction, roughly parallel
to the axis of the helix.
o The C=O groups of peptide bonds point
in the opposite direction, also roughly
parallel to the axis of the helix.
o 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.
o All R- groups point outward from the
helix.
• b-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.
➔ In a section of b-pleated sheet;
o 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.
o All R- groups on any one chain
alternate, first above, then below the
plane of the sheet, etc.
• Random coil: no fix structure
• Many globular proteins contain all three
kinds of secondary structure in different
parts of their molecules: -helix, -pleated
sheet, and random coil (next screen).
➔ Example is enzyme carboxypeptidase.
• The collagen triple helix contains three a-
helixes
III. Tertiary structure: The complete three-
dimensional arrangement of atoms of a
polypeptide chain.
• Tertiary structure: the overall
conformation of an entire polypeptide
chain.
• Tertiary structure is stabilized in four ways:
o Covalent bonds as for example, the
formation of disulfide bonds between
cysteine side chains.
o Hydrogen bonding between polar
groups of side chains, as for example
between the -OH groups of serine and
threonine.
o Salt bridges, as for example, the
attraction of the -NH3+ group of lysine
and the -COO- group of aspartic acid.
o Hydrophobic interactions, as for
example, between the nonpolar side
chains of phenylalanine and isoleucine.
IV. Quaternary structure: The spatial relationship
and interactions between subunits in a
protein that has more than one polypeptide
chain.
• 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.
 1. Hemoglobin insoluble salts with -SH groups; Hg2+ for
o Adult hemoglobin: Two alpha chains of example forms -S-Hg-S-.
141 amino acids each, and two beta • Alcohols: 70% ethanol penetrates
chains of 146 amino acids each. bacteria and kills them by coagulating
o Fetal hemoglobin: Two alpha chains and their proteins. It is used to sterilize skin
two gamma chains. Fetal hemoglobin before injections.
has a greater affinity for oxygen than
does adult hemoglobin.
o Each chain surrounds an iron-containing
heme unit.
2. Collagen
• Tropocollagen: triple helix units,
constitute the soluble form of collagen,
found only in fetal and young connective
tissues
• With aging, the triple helixes that organize
themselves into fibrils crosslink and form
insoluble collagen, crosslinking involves
covalent bonds that link 2 lysine residues
together
3. 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.

DENATURATION
• 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.
• 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-