Proteins
Proteins
Dr. Gyebi A. G
Biochemistry Department
Bingham University Karu.
Proteins (Greek proteios, ―primary‖ or ―of first importance‖) are biochemical molecules
consisting of polypeptides joined by peptide bonds between the amino and carboxyl groups of
amino acid residues.
The repeating units in peptide is called amino acid residue. Proteins are polypeptides that are
made up of 40-100 amino acids
Proteins are the indispensable agents of biological function, and amino acids are the building
blocks of proteins. The stunning diversity of the thousands of proteins found in nature arises
from the intrinsic properties of only 20 commonly occurring amino acids. These features include
(1) the capacity to polymerize, (2) novel acid–base properties, (3) varied structure and chemical
functionality in the amino acid side chains, and (4) chirality.
The structure of a single typical amino acid is shown in Figure 1. Central to this structure is the
tetrahedral alpha (α) carbon (C), which is covalently linked to both the amino group and the
carboxyl group. Also bonded to this -carbon is a hydrogen and a variable side chain (R). It is
the side chain, the so called R group that gives each amino acid its identity. It is sufficient for
now to realize that, in neutral solution (pH 7), the carboxyl group exists as -COO- and the amino
group as -NH3+. Because the resulting amino acid contains one positive and one negative charge,
it is a neutral molecule called a zwitterion. Amino acids are also chiral molecules. With four
different groups attached to it, the -carbon is said to be asymmetric. The two possible
configurations for the -carbon constitute non identical mirror image isomers or enantiomers.
Figure: 1 Structure of an Amino Acid Skeleton
A. Amino acids share Common structural features.
i. C atom center, Amino group on one side carboxylic acid on the other, and an R group that can
be H or more complicated will explore in a minute.
ii. 20 common AA called standard AA’s other AA‘s derived from these AA‘s usually by post-
translational modification (ie AA was changed after it was made into a protein)
iii. All 20 AA‘s have trivial names
All have a 3 letter code
All have a 1 letter code
I expect you to know codes and structures for all AA‘s
Naming substituents on AA‘s is not standard organic chem. base C is called alpha C then out
from there is beta, gamma, delta, epsilon.
iv. All AA‘s expect Glycine are chiral.
All AA‘s expect Glycine have 4 different constituents around Cá.
Why is this important?
Chiral center non-superimposable mirror images enantiomers optically active
(Will rotate plane polarized light and display differential absorbtion of circularly polarized light)
Characteristics of Proteins
Acid-Base Properties
• Proteins take the form of zwitterions. They have characteristic isoelectric points, and can
behave as buffers in solutions.
• The tendency for large molecules to remain in solution or form stable colloidal dispersions
depends on the repulsive forces acting between molecules with like charges on their surfaces.
– When proteins are at a pH in which there is a net positive or negative charge, the like charges
cause the molecules to repel one another, and they remain dispersed.
– When the pH is near the isoelectric point, the net charge on the molecule is zero, and the
repulsion between proteins is small. This causes the protein molecules to clump and precipitate
from solution
Zwitterions
• Because amino acids contain both an acidic and a basic functional group, an internal acid-base
reaction occurs, forming an ion with both a positive and anegative charge called a zwitterions.
In solution, the structure of an amino acid can change with the pH of the solution
Since the pH of the solution affects the charge on the amino acid, at some pH, the amino acid
will form a zwitterion. This is called the isoelectric point.
• Each amino acid (and protein) has a characteristic isoelectric point: those with neutral R groups
are near a pH of 6, those with basic R groups have higher values, and those with acidic R groups
have lower values.
• Because amino acids can react with both H3O+ and OH-, solutions of amino acids and proteins
can act as buffers. (E.g., blood proteins help to regulate the pH of blood.
Reaction of Amino acids:
Amino acids can undergo any of the reactions characteristic of the functional groups in the
structure.
• Cysteine is the only amino acid that contains a sulfhydryl (thiol, R—SH) group. Thiols are
easily oxidized to form disulfide bonds (R—S—S—R).
This allows cysteine to dimerize to form cystine:
Peptide Formation
Peptide Bond
The crucial feature of amino acids that allows them to polymerize to form peptides and proteins
is the existence of their two identifying chemical groups: the amino (-NH3+) and carboxyl (-
COO-) groups, The amino and carboxyl groups of amino acids can react in a head-to-tail fashion,
eliminating a water molecule and forming a covalent amide linkage, which, in the case of
peptides and proteins, is typically referred to as a peptide bond. The equilibrium for this
reaction in aqueous solution favors peptide bond hydrolysis. For this reason, biological systems
as well as peptide chemists in the laboratory must carry out peptide bond formation in an indirect
manner or with energy input.
Iteration of the reaction shown in Figure 2 produces polypeptides and proteins. The remarkable
properties of proteins, all depend in one way or another on the unique properties and chemical
diversity of the 20 common amino acids found in proteins.
Amino acids are linked together by ‗amide groups’ called peptide bonds.
During protein synthesis, the carboxyl group of amino acid at the end of the growing
polypeptide chain reacts with the amino group of an incoming amino acid, releasing a
molecule of water. The resulting bond between the amino acids is a peptide bond.
Proteins come in many different shapes and sizes. Some are globular (roughly spherical) in
shape, whereas others form long, thin fibers. For example, the hemoglobin protein that carries
oxygen in the blood is a globular protein, while collagen, found in our skin, is a fibrous protein.
A protein‘s shape is critical to its function, and, as we‘ll see in the next article, many different
types of chemical bonds may be important in maintaining this shape. Changes in temperature and
pH, as well as the presence of certain chemicals, may disrupt a protein‘s shape and cause it to
lose functionality, a process known as denaturation.
• Amides can be thought of as forming from the reaction of an amine and a carboxylic acid:
• In the same way, two amino acids can combine to form a dipeptide, held together by a peptide
bond:
The two amino acids can connect the other way as well, forming a structural isomer of the
dipeptide, with a unique set of physical properties:
• A third amino acid can join the chain to form a tripeptide:
A fourth amino acid would form a tetrapeptide, a fifth would form a pentapeptide, and so on.
• Short chains are referred to as peptides, chains of up to about 50 amino acids are polypeptides,
and chains of more than 50 amino acids are proteins.
(The terms protein and polypeptide are often used interchangeably.)
• Amino acids in peptide chains are called amino acid residues.
– The residue with a free amino group is called the N-terminal residue, and is written on the left
end of the chain.
– The residue with a free carboxylate group is called the C-terminal residue, and is written on
the right end of the chain
Peptides are named by starting at the N-terminal end and listing the amino acid residues from left
to right.
• Large amino acid chains are unwieldy to draw in their complete forms, so they are usually
represented by their three-letter abbreviations, separated by
dashes:
– Gly-Ala (Gly = N-terminal, Ala = C-terminal)
– Ala-Gly (Ala = N-terminal, Gly = C-terminal)
• The tripeptide alanylglycylvaline can be written as Ala-Gly-Val. (There are five other
arrangements of these amino acids that are possible.)
• Insulin has 51 amino acids, with 1.551066 different possible arrangements, but the body
produces only one.
Nonapeptide proteins
Adrenocorticotropic hormone
• Adrenocorticotropic hormone (ACTH) is a 39-residue peptide produced in the pituitary gland.
It regulates the production of steroid hormones in the cortex of the adrenal gland.
Size of Proteins
• Proteins are very large polymers of amino acids with molecular weights that vary from 6000
amu to several million amu.
– Glucose (C6H12O6) = 180 amu
– Hemoglobin (C2952H4664O832N812S8Fe4) = 65,000 am
Proteins are too large to pass through cell membranes, and are contained within the cells where
they were formed unless the cell is damaged by disease or trauma.
– Persistent large amounts of protein in the urine are indicative of damaged kidney cells.
– Heart attacks can also be confirmed by the presence of certain proteins in the blood that are
normally confined to cells in heart tissue.
Each protein has a unique sequence of amino acid residues that cause it to fold into a distinctive
shape that allows the protein to function properly.
• Primary structure of human insulin:
Secondary Structure —
The a Helix
• Hydrogen bonding causes protein chains to fold and align to produce orderly patterns called
secondary structures.
The a-helix is held in this shape by hydrogen bonding interactions between amide groups, with
the side chains extending outward from the coil.
• The amount of a-helix coiling in proteins is highly variable
In a-keratin (hair, pictured below), myosin (muscles), epidermin (skin), and fibrin (blood clots),
two or more helices coil together (supracoiling) to form cables. These cables make up bundles
of fibers that strengthen tissues in which they are found:
Hydrogen bonding also influences the secondary structure, but here the hydrogen bonding is
between R groups, while in secondary structures it is between the C=O and NH portions of the
backbone.
4. Hydrophobic interactions result from the attraction of nonpolar groups, or when they are
forced together by their mutual repulsion of the aqueous solvent.
These interactions are particularly important between the benzene rings in phenylalanine or
tryptophan. This type of interaction is relatively
weak, but since it acts over large surface areas, the net effect is a strong interaction.
4. cont. The compact structure of globular proteins in aqueous solution, in which the nonpolar
groups are pointed inward, away from the water molecules.
Quaternary Structure of Proteins
• When two or more polypeptide chains are held together by disulfide bridges, salt bridges,
hydrogen bond, or hydrophobic interactions, forming a larger protein complex.
• Each of the polypeptide subunits has its own primary, secondary, and tertiary structure.
• The arrangement of the subunits to form a larger protein is the quaternary structure of the
protein.
Hemoglobin
• Hemoglobin is made of four subunits: two identical alpha chains containing 141 AA‘s and two
identical beta chains containing 146 AA‘s. Each subunit contains a heme group located in
crevices near the exterior of the molecule
Denaturation
• Proteins are maintained in their native state (their natural 3D conformation) by stable
secondary and tertiary structures, and by aggregation of subunits into quaternary structures.
• Denaturation is caused when the folded native structures break down because of extreme
temps. Or pH values, which disrupt the stabilizing structures.
The structure becomes random and disorganized.
Denaturation
• Most proteins are biologically active only over a temperature range of 0ºC to 40ºC.
• Heat is often used to kill microorganisms and deactivate their toxins. The protein toxin from
Clostridium botulinum is inactivated by being heated to 100ºC for a few minutes; heating also
deactivates the toxins that cause diphtheria and tetanus.
• Heat denaturation is used to prepare vaccines against some diseases. The denatured toxin can
no longer cause the disease, but it can stimulate the body to
produce substances that induce immunity.
Denaturation
• Proteins can also be denatured by heavy-metal ions such as Hg2+, Ag+, and Pb2+ hat interact
with —SH and carboxylate groups.
– Organic materials containing Hg (mercurochrome and merthiolate) were common topical
antiseptics.
– Heavy-metal poisoning is often treated with large doses of raw egg white and milk; the
proteins in the egg and milk bind to the metal ions, forming a precipitate, which is either vomited
out or pumped out
Reference Books
1) Harper‘s Illustrated Biochemistry-30th edition
2) Textbook of Biochemistry with Clinical Correlations. 4th edition. Thomas M. Devlin.
3) Biochemistry. 4th edition. Donald Voet and Judith G. Voet.
4) Biochemistry 7th edition by Jeremy M. Berg, John L. Tymoczko and Lubert Stryer
5) Lehninger Principles of Biochemistry
6) Netter's essential biochemistry 1st Ed
7) https://en.wikipedia.org/wiki/aminoacids