Biochemistry I

3rd stage
Lecture: 3 Dr. Shaimaa Munther

STRUCTURE OF PROTEIN
 OVERVIEW
 The 20 amino acids commonly found in proteins are joined together by peptide
bonds.
 The linear sequence of the linked amino acids contains the information necessary
to generate a protein molecule with a unique three-dimensional shape.
 The complexity of protein structure is best analyzed by considering the molecule
in terms of four organizational levels, namely: Primary, Secondary, Tertiary &
Quaternary.
Why knowing protein structure is important?
A protein’s function depends on its specific conformation. In almost every case,
the function depends on its ability to recognize and bind to some other molecule.
For example, antibodies bind to particular foreign substances that fit their binding
sites. Enzyme recognize and bind to specific substrates, facilitating a chemical
reaction.
Note:
 A functional protein consists of one or more polypeptides that have been
precisely twisted, folded, and coiled into a unique shape.
 It is the order of amino acids that determines what the three-dimensional
conformation will be.

Levels of Protein Structure

1. Primary Structure of Protein:
The primary structure of proteins involves the sequence of amino acids in a
polypeptide chain.
Understanding the primary structure of proteins is important because many
genetic diseases result in proteins with abnormal amino acid sequences, which
cause improper folding and loss or impairment of normal function.
Thus, studying the poly peptide chain means studying the primary structure of
protein

A. Peptide bond
In proteins, amino acids are joined covalently by peptide bonds. Peptide bond are
amide linkages between the α-carboxyl group of one amino acid and the α-amino
group of another. For example, valine and alanine can form the dipeptide
valylalanine through the formation of a peptide bond.
 Biochemistry I
3rd stage
Lecture: 3 Dr. Shaimaa Munther

B. Characteristics of the peptide bond:

 The peptide bond has a partial double-bond character, that is, it is shorter
than a single bond, and is rigid and planar.
 The peptide bond is generally a trans bond (instead of cis) in large part
because of steric interference of the R-groups when in the cis position.
 Peptide bonds are not broken by conditions that denature proteins, such as
heating & high concentrations of urea.
 Prolonged exposure to a strong acid or base at elevated temperatures is
required to hydrolyze these bonds non enzymically.
C. Naming the peptide:
 By convention, the free amino end (N-terminal) of the peptide chain is
written to the left and the free carboxyl end (C-terminal) to the right.
Therefore, all amino acid sequences are read from the N- to the C-terminal
end of the peptide. For example, in the previous figure the order of the
amino acids is “valine, alanine.”
 Linkage of many amino acids through peptide bonds results in an
unbranched chain called a polypeptide.
 Each component amino acid in a polypeptide is called a “residue” because
it is the portion of the amino acid remaining after the atoms of water are
lost in the formation of the peptide bond.
 When a polypeptide is named, all amino acid residues have their suffixes
(-ine, -an, -ic, or -ate) changed to -yl, with the exception of the C-terminal
amino acid. For example, a tripeptide composed of an N-terminal valine, a
glycine, and a C-terminal leucine is called valyl glycyl leucine.
 Biochemistry I
3rd stage
Lecture: 3 Dr. Shaimaa Munther

2.Secondary Structure of Proteins:

 The secondary structure of the polypeptide is a three-dimensional structure.
 It results from hydrogen bond formation between hydrogen of –NH group
of peptide bond and the carbonyl oxygen –C=O of another peptide bond.
 According to H-bonding there are two main forms of secondary structure:

1. α-helix:
 α-helix is a spiral structure, consisting of a tightly packed, coiled
polypeptide backbone core, with the side chains of the component
amino acids extending outward from the central axis to avoid interfering
sterically with each other.
 Formed by a H-bond between every 4th peptide bond – C=O to N-H
 Usually found in proteins that span a membrane
 The  helix can either coil to the right or the left.
 Each turn of an α-helix contains 3.6 amino acids.
 Proline disrupts an α-helix because its secondary amino group is not
geometrically compatible with the right-handed spiral of the α-helix.
 Example of proteins contains α-helices: keratins are a fibrous protein.
They are a major component of tissues such as hair and skin.
Myoglobin, a globular, flexible protein molecule

2. β-sheets:
 It is another form of secondary structure in which two or more
polypeptides (or segments of the same peptide chain) are linked
together by hydrogen bond between H- of NH- of one chain and
carbonyl oxygen of adjacent chain (or segment).
 In β-sheet all of the peptide bond components are involved in hydrogen
bonding.
 Unlike the α-helix, β-sheets are composed of two or more peptide
chains (β-strands), or segments of polypeptide chains, which are almost
fully extended.
 The surfaces of β-sheets appear “pleated,” and these structures are,
therefore, often called “β-pleated sheets.”
 Biochemistry I
3rd stage
Lecture: 3 Dr. Shaimaa Munther

3. Tertiary structure of globular proteins

 The three-dimensional arrangement of protein structure is referred to as
tertiary structure. It is a compact structure with hydrophobic side chains held
interior while the hydrophilic groups are on the surface of the protein
molecule. This type of arrangement ensures stability of the molecule.
 Bonds of tertiary structure: Besides the hydrogen bonds, disulfide bonds (-
S-S-), ionic interactions (electrostatic bonds), hydrophobic interactions and
van der Waals forces also contribute to the tertiary structure of proteins.
 Domain: a compact and self-folding component of the protein that usually
represents a discreet structural and functional unit. Polypeptide chains that
are greater than 200 amino acids in length generally consist of two or more
domains.
 Biochemistry I
3rd stage
Lecture: 3 Dr. Shaimaa Munther

4. QUATERNARY STRUCTURE OF PROTEINS

 Many proteins consist of a single polypeptide chain, and are defined as
monomeric proteins. However, others may consist of two or more
polypeptide chains that may be structurally identical or totally
unrelated.
 The arrangement of these polypeptide subunits is called the quaternary
structure of the protein. Subunits are held together by noncovalent
interactions (for example, hydrogen bonds, ionic bonds, and
hydrophobic interactions).
 Collagen is a fibrous protein of three polypeptides that are supercoiled
like a rope.
 Hemoglobin is a globular protein with two copies of two kinds of
polypeptides.
 Subunits may either function independently of each other, or may work
cooperatively, as in hemoglobin, in which the binding of oxygen to one
subunit of the tetramer increases the affinity of the other subunits for
oxygen.

Note:
 Any protein consisting of a single polypeptide chain is not in the
quaternary structure and, is defined as monomeric protein.
 If there are two subunits, the protein is quaternary and is called
"dimeric", if three subunits "trimeric", and, if several subunits,
"multimeric."
 Biochemistry I
3rd stage
Lecture: 3 Dr. Shaimaa Munther

Denaturation and Misfolding of Proteins

 Protein denaturation results in the unfolding and disorganization of the

protein’s secondary and tertiary structures, which are not accompanied
by hydrolysis of peptide bonds.
 Denaturing agents include heat, organic solvents, mechanical mixing,
strong acids or bases, detergents, and ions of heavy metals such as lead
and mercury.
 Denaturation may, under ideal conditions, be reversible, in which case
the protein refolds into its original native structure when the denaturing
agent is removed. However, most proteins, once denatured, remain
permanently disordered.
 Denatured proteins are often insoluble and, therefore, precipitate from
solution.

Protein Classification
1. Fibrous Protein
 Polypeptides arranged in long strands or sheets
 Water insoluble (lots of hydrophobic AA’s)
 Strong but flexible
 Structural protein or contractile proteins (keratin, collagen, muscle,
microtubules, cytoskeleton, mitotic spindle, cilia, flagella)

2. Globular Protein
 Polypeptide chains folded into spherical or globular form
 Water soluble
 Contain several types of secondary structure
 Diverse functions (enzymes, hemoglobin, immunoglobulins, membrane
receptor sites regulatory proteins)