Proteins

Proteins
• A large biological molecule
made of many amino acids
linked together through amide
(peptide) bonds.
• is a naturally occurring,
unbranched polymer in which
the monomer units are amino
acids.
 Functions of Protein
• Structure. The main structural material for plants is cellulose.
For animals, it is structural proteins, which are the chief
constituents of skin, bones, hair, and nails. Two important
structural proteins are collagen and keratin.

• Catalysis. Virtually all the reactions that take place in living

organisms are catalyzed by proteins called enzymes. Without
enzymes, the reactions would take place so slowly as to be
useless
 Functions of Protein
• Movement Every time we crook a finger, climb stairs, or blink
an eye, we use our muscles. Muscle expansion and
contraction are involved in every movement we make.
Muscles are made up of protein molecules called myosin and
actin.
• Transport A large number of proteins perform transportation
duties. For example, hemoglobin, a protein in the blood,
carries oxygen from the lungs to the cells in which it is used
and carbon dioxide from the cells to the lungs. Other proteins
transport molecules across cell membranes.
 Functions of Protein
• Hormones Many hormones are proteins, including insulin,
erythropoietin, and human growth hormone.
• Protection When a protein from an outside source or some
other foreign substance (called an antigen) enters the body,
the body makes its own proteins (called antibodies) to
counteract the foreign protein. Blood clotting is another
protective function carried out by a protein, this one called
fibrinogen.
 Functions of Protein
• Storage Some proteins store materials in the way that
starch and glycogen store energy. For example, casein in
milk and ovalbumin in eggs store nutrients for newborn
mammals and birds. Ferritin, a protein in the liver, stores
iron.
• Regulation Some proteins not only control the expression
of genes, thereby regulating the kind of proteins
synthesized in a particular cell, but also dictate when such
manufacture takes place
 Amino Acid
• An amino acid is an organic
compound that contains both an
amino (-NH2) group and a carboxyl
(-COOH) group. The amino acids
found in proteins are always α-amino
acids. An α-amino acid is an amino
acid in which the amino group and the
carboxyl group are attached to the
a-carbon atom.
• The R group present in an α-amino
acid is called the amino acid side
chain.
 Amino Acids
• More than 700 different naturally occurring amino acids are
known, but only 20 of them, called standard amino acids, are
normally present in proteins. A standard amino acid is one
of the 20 a-amino acids normally found in proteins.
– A nonpolar amino acid is an amino acid that contains one amino group, one
carboxyl group, and a nonpolar side chain.
– A polar neutral amino acid is an amino acid that contains one amino group, one
carboxyl group, and a side chain that is polar but neutral.
– A polar acidic amino acid is an amino acid that contains one amino group and two
carboxyl groups, the second carboxyl group being part of the side chain.
– A polar basic amino acid is an amino acid that contains two amino groups and one
carboxyl group, the second amino group being part of the side chain.
Acid-Base Properties of Amino Acids
• Amino acids contain both an acidic
group,-COOH, and a basic –NH2 group.
These two groups can undergo an
intramolecular acid-base reaction. The
result is a transfer of the hydrogen from the
-COOH group to the –NH2 group to form a
dipolar ion, an ion that has one positive
charge and one negative charge and is thus
electrically neutral. Dipolar ions are known
as zwitterions
• A zwitterion is a molecule that has a
positive charge on one atom and a negative
charge on another atom, but which has no
net charge
 Acid Base Properties of Amino Acids
• Zwitterion structure changes when the pH of a solution containing
an amino acid is changed from neutral either to acidic (low pH) by
adding an acid such as HCl or to basic (high pH) by adding a base
such as NaOH.
– In an acidic solution, the zwitterion accepts a proton (H+) to form a positively
charged ion.
– In basic solution (high pH), amino acid zwitterions lose protons from their acidic
–NH3+ groups to leave only the negatively charged COO- groups: -
 Acid-Base Properties of Amino Acids
• Thus, in a solution, three different amino acid forms can exist
(zwitterion, negative ion, and positive ion). The three species are
actually in equilibrium with each other, and the equilibrium shifts
with pH change. The overall equilibrium process can be
represented as follows:
 Acid-Base Properties of Amino Acids
• Amino acids are never present in the completely nonionized form
in either the solid state or aqueous solution. The charge of an
amino acid molecule at any given moment depends on the
particular amino acid and the pH of the medium. The pH at which
the net positive and negative charges are evenly balanced is the
amino acid’s isoelectric point (pI)
• Isoelectric point (pI) The pH at which a sample of an amino acid
has equal numbers of + and - charges.
 Isoelectric
Points for the
20 Amino
Acids
Commonly
Found in
Proteins
 Peptides
• Under proper conditions, amino acids can bond together to produce an
unbranched chain of amino acids. The length of the amino acid chain can vary
from a few amino acids to many amino acids. Such a chain of covalently linked
amino acids is called a peptide. A peptide is an unbranched chain of amino
acids.
– Peptides are further classified by the number of amino acids present in the chain. A
compound containing two amino acids is specifically called a dipeptide; three amino
acids joined together in a chain constitute a tripeptide; and so on. A polypeptide is a
long unbranched chain of amino acids.
 Nature of the Peptide Bond
• The bonds that link amino acids together in a peptide chain are called
peptide bonds. This is the formation of the amino (–NH2) group of one
amino acid and the carboxyl (-COOH) group of a second amino acid.
Removal of the elements of water from the reacting carboxyl and amino
groups and the ensuing formation of the amide bond is better visualized
when expanded structural formulas for the reacting groups are used. The
general equation for this reaction is:
 Nature of the Peptide Bond
• In all peptides, long or short, the amino acid at one end of the amino
acid sequence has a free NH3+ group, and the amino acid at the other
end of the sequence has a free COO- group. The end with the free
NH3+ group is called the N-terminal end, and the end with the free
COO- group is called the C-terminal end.
• The individual amino acids within a peptide chain are called amino acid
residues. An amino acid residue is the portion of an amino acid
structure that remains, after the release of H2O, when an amino acid
participates in peptide bond formation as it becomes part of a peptide
chain
Nature of the Peptide Bond
 Drawing Peptide bond structures
Draw the structural formula for the tripeptide Ala–Gly–Val.
 Drawing Peptide bond structures
• Draw the structural formula for the tripeptide Ala–Gly–Val.
 Drawing Peptide bond structures
• Draw the structural formula for the tripeptide Ala–Gly–Val.
Exercise: Drawing Peptide bond structures
• Draw the structural formula for the tripeptide Cys-Ala-Gly.
 Peptide Nomenclature
• Small peptides are named as derivatives of the C-terminal amino
acid that is present. The IUPAC rules for doing this are:
– Rule 1: The C-terminal amino acid residue (located at the far right of the
structure) keeps its full amino acid name.
– Rule 2: All of the other amino acid residues have names that end in -yl. The
–yl suffix replaces the -ine or -ic acid ending of the amino acid name, except
for tryptophan (tryptophyl), cysteine (cysteinyl), glutamine (glutaminyl), and
asparagine (asparaginyl).
– Rule 3: The amino acid naming sequence begins at the N-terminal amino
acid residue.
 Exercise: Peptide nomenclature
• Assign IUPAC names to each of the following small
peptides.
a. Glu–Ser–Ala -GlutamylSerylAlanine
b. Gly–Tyr–Leu–Val- GlycylTyrosylLeucylValine
 Structures of Proteins
• Proteins have four levels of structure:
– Primary structure
– Secondary structure
– Tertiary structure
– Quaternary structure
 Primary Structure
• Primary protein structure is the order in which amino
acids are linked together in a protein. Every protein has its
own unique amino acid sequence. Primary protein
structure always involves more than just the numbers and
kinds of amino acids present; it also involves the order of
attachment of the amino acids to each other through
peptide bonds.
Primary structure of Myoglobin and Insulin
 Secondary Structure
• Secondary protein structure is the arrangement in
space adopted by the backbone portion of a protein. The
two most common types of secondary structure are the
alpha helix (α-helix) and the beta-pleated sheet (β-pleated
sheet).
 Alpha Helix
• An alpha helix structure is a protein secondary structure
in which a single protein chain adopts a shape that
resembles a coiled spring (helix), with the coil
configuration maintained by hydrogen bonds.
 Alpha Helix
• Further details about the alpha helix secondary protein structure
are:
– The twist of the helix forms a right-handed, or clockwise, spiral.
– The hydrogen bonds between C=O and N-H entities are orientated parallel to
the axis of the helix
– A given hydrogen bond involves a C=O group of one amino acid and a N-H
group of another amino acid located four amino acid residues further along
the spiral This is because one turn of the spiral includes 3.6 amino acid
residues.
– All of the amino acid R groups extend outward from the spiral There is not
enough room for the R groups within the spiral.
Alpha Helix
 Beta Pleated Sheet
• A beta-pleated sheet structure is a protein secondary structure in which
two fully extended protein chain segments in the same or different
molecules are held together by hydrogen bonds. The term pleated sheet
arises from the repeated zigzag pattern in the structure
• In molecules where the β-pleated sheet involves a single molecule,
several U-turns in the protein chain arrangement are needed in order to
form the structure.
 Beta Pleated Sheet
• Further features of the β pleated sheet secondary protein
structure are:
– The hydrogen bonds between C=O and N-H entities lie in the
plane of the sheet.
– The amino acid R groups are found above and below the plane
of the sheet and within a given backbone segment alternating
between the top and bottom positions
Beta Pleated Sheet
 Tertiary Structure
• Tertiary protein structure is the overall
three-dimensional shape of a protein that results from the
interactions between amino acid side chains (R groups)
that are widely separated from each other within a peptide
chain.
 Tertiary Structure
• In general, tertiary structures are stabilized in five ways:
– Covalent Bonds The covalent bond most often involved in the stabilization of
the tertiary structure of proteins is the disulfide bond.
– Hydrogen Bonding Tertiary structures are stabilized by hydrogen bonding
between polar groups on side chains or between side chains and the peptide
backbone
– Salt Bridges Salt bridges, also called electrostatic attractions, occur between
two amino acids with ionized side chains —that is, between an acidic amino
acid (-COO-) and a basic amino acid (-NH3+ or =NH2+) side chain. The two
are held together by simple ion–ion attraction
 Tertiary Structure
• In general, tertiary structures are stabilized in five ways:
– Hydrophobic Interactions In an aqueous solution, globular proteins usually turn
their polar groups outward, toward the aqueous solvent, and their nonpolar groups
inward, away from the water molecules. The nonpolar groups prefer to interact with
each other, excluding water from these regions. The result is a series of hydrophobic
interactions
– Metal Ion Coordination Two side chains with the same charge would normally repel
each other, but they can also be linked via a metal ion. For example, two glutamic
acid side chains (-COO-) would both be attracted to a magnesium ion (Mg2+), forming
a bridge
Tertiary Structure
 Quaternary Structure
• Quaternary structure is the highest
level of protein organization. It is
found only in multimeric proteins
Such proteins have structures
involving two or more peptide
chains that are independent of
each other—that is, are not
covalently bonded to each other.
Quaternary protein structure is
the organization among the
various peptide chains in a
multimeric protein.
Structure of
Proteins
 Protein Denaturation
• Protein denaturation is the partial or complete disorganization of
a protein’s characteristic three-dimensional shape as a result of
disruption of its secondary, tertiary, and quaternary structural
interactions. Because the biochemical function of a protein
depends on its three-dimensional shape, the result of denaturation
is loss of biochemical activity. Protein denaturation does not affect
the primary structure of a protein.
 Protein Denaturation
• Agents that cause denaturation include heat, mechanical agitation,
detergents, organic solvents, extremely acidic or basic pH, and
inorganic salts.
– Heat The weak side-chain attractions in globular proteins are easily disrupted by
heating, in many cases only to temperatures above 50 °C. Cooking meat converts
some of the insoluble collagen into soluble gelatin, which can be used in glue and for
thickening sauces.
– Mechanical agitation The most familiar example of denaturation by agitation is the
foam produced by beating egg whites. Denaturation of proteins at the surface of the
air bubbles stiffens the protein and causes the bubbles to be held in place.
– Detergents Even very low concentrations of detergents can cause denaturation by
disrupting the association of hydrophobic side chains.
 Protein Denaturation
• Agents that cause denaturation include heat, mechanical agitation,
detergents, organic solvents, extremely acidic or basic pH, and inorganic
salts.
– Organic compounds Polar solvents such as acetone and ethanol interfere with
hydrogen bonding by competing for bonding sites. The disinfectant action of ethanol,
for example, results from its ability to denature the bacterial protein.
– pH changes Excess H+ or OH- ions react with the basic or acidic side chains in
amino acid residues and disrupt salt bridges. One familiar example of denaturation
by pH change is the protein coagulation that occurs when milk turns sour because it
has become acidic.
– Inorganic salts Sufficiently high concentrations of ions can disturb salt bridges
 Protein Denaturation
• Most denaturation is
irreversible: Hard-boiled
eggs do not soften when
their temperature is lowered.
Many cases are known,
however, in which unfolded
proteins spontaneously
undergo renaturation a
return to their native state
when placed in a
non-denaturing medium
Reference and Photo credits
• McMurry,J & Castellion, M.E., Ballantine, D.S., Hoeger, C.,
Peterson, V.E. (2010). Essentials of General, Organic and
Biological Chemistry (6th ed.).Pearson Prentice Hall.
• Bettelheim, F.A., Brown, W.H., Campbell, M.K., Farell, S.O. &
Torres, O.J. (2013). Introduction to General, Organic, and
Biochemistry (10th ed.). Cengage Learning. US
• Stoker, S.H (2013). General, Organic, and Biological Chemistry
(6th ed.). Brooks Cole. Cengage Learning. US