NUR 112

Medical
Biochemistry I

Lecture 3: Proteins
Dr. Shaviya
PROTEINS
Proteins are natural substances with high molecular weights ranging from 5,000 to many millions. Besides Carbon,
Hydrogen and Oxygen, they also contain Nitrogen, and sometimes, Sulfur and Phosphorous.

Proteins are most important constituent of cell membranes and cytoplasm. Muscle and blood plasma also contain
certain specific proteins.

Definition
Proteins are macromolecules with a backbone formed by polymerization of amino acids in a polyamide structure.

Classification
Proteins may be classified on the basis of their composition, solubility, shape, biological function and on their 3D
structure.

I. Composition: -
A. Simple protein:
Yields only amino acids and no other major organic or inorganic hydrolysis products i.e. most of the elemental
compositions.
B. Conjugated Proteins
Yields amino acids and other organic and inorganic components. Examples
Nucleoprotein (a protein containing Nuclei acids)
Lipoprotein (a protein containing lipids)
Phosphoprotein (a protein containing phosphorous)
Metalloprotein (a protein containing metal ions of Fe2+)
Glycoprotein (a protein containing carbohydrates

II. Solubility
a) Albumins: These proteins such as egg albumin and serum albumin are readily soluble in water and coagulated
by heat.
b) Globulins: these proteins are present in serum, muscle and other tissues and are soluble in dilute salt solution
but sparingly in water.
c) Histones: Histones are present in glandular tissues (thymus, pancreas etc.) soluble in water; they combine with
nucleic acids in cells and on hydrolysis yield basic amino acids.
III. Overall Shape
A. Fibrous proteins
In these proteins, the molecules are constituted by several coiled cross-linked polypeptide chains, they are insoluble
in water and highly resistant to enzyme digestion. They include:
1. Collagens: the major protein of the connective tissue, insoluble in water, acids or alkalis. But they are convertible
to water-soluble gelatin, easily digestible by enzymes.
2. Elastins: present in tendons, arteries and other elastic tissues, not convertible to gelatin.
3. Keratins: protein of hair, nails etc.
B. Globular proteins: These are globular or ovoid in shape, soluble in water and constitute the enzymes, oxygen
carrying proteins, hormones etc. the axial ratio is 3 to 4 or less. Subclasses include: - Albumin, globulins and
histones.
IV. Biological Functions:
Proteins are sometimes described as the "workhorses" of the cell because they do So many things Like:
Enzymes: kinases, transaminases etc.
Storage proteins: myoglobin, ferretin
Regulatory proteins: peptide hormones, DNA binding proteins
Structural protein: collagen, proteoglycan
Protective proteins: blood clotting factors, Immunoglobins,
Transport protein: Hemoglobin, plasma lipoproteins
Contractile or motile Proteins: Actin, tubulin
V. On their level of organization

Primary, secondary, tertiary and quaternary.

a)Primary Structure of Proteins

•The primary structure of a protein is defined by the linear sequence of amino acid residues.

•Proteins typically contain between 50 and 2000 amino acid residues.

•The mean molecular mass of an amino acid residue is about 110 Dalton units (Da).

•Therefore, the molecular mass of most proteins ranges between 5500 and 220,000 Da.
• The amino acid composition of a peptide chain profoundly affects the physical and chemical
properties of proteins.

• Proteins rich in polar amino acids are more water-soluble.

• Proteins rich in aliphatic or aromatic amino groups are relatively insoluble in water but more
soluble in cell membranes, allowing them to easily cross the cell membrane.

• The primary structure of a protein does not represent its 3D nature, as the extended chain of
amino acids is co-planar due to the rigidity of the covalent peptide bond.
b) Secondary Structure
Refers to the local structure of a polypeptide chain in a protein.

Determination: This structure is determined by hydrogen bonds.

Interactions: Occur between the carbonyl oxygen group of one peptide bond and the amide
hydrogen of another nearby peptide bond.
Alpha (∝) helix
Types of Secondary Structure:

Alpha (∝) helix

Beta (β) pleated sheet
α-Helix Structure:
The α-helix is a rod-like structure with peptide chains tightly coiled.

Side Chains: The side chains of amino acid residues extend outward from the axis of the spiral.

Hydrogen Bonding:
•Each amide carbonyl group is hydrogen-bonded to the amide hydrogen of a peptide bond that is 4 residues away
along the same chain.

•This bonding involves nearly every =NH group binding with a carbonyl oxygen, fourth in line behind the primary
structure.

Helix Characteristics:
•There are 3.6 amino acid residues per turn of the helix.

•A complete turn has a 0.54 nm pitch (1 nm = 10^-9 m).

•The helix winds in a right-handed manner in almost all-natural proteins, turning in a clockwise fashion around the
axis.
β-Pleated Sheet Structure:

• The β-pleated sheet is an extended structure, in contrast to the coiled α-helix.

• The sheet is "pleated" because the carbon-carbon (C-C) bonds are tetrahedral and cannot exist in a planar
configuration.

Types of β-Pleated Sheets:

Parallel β-Sheet: Formed when the polypeptide chains run in the same direction.
Antiparallel β-Sheet: Formed when the polypeptide chains run in opposite directions.
A single protein molecule may contain both types of β-sheet configurations in different parts of its structure.

Amino Acids in β-Sheets:

•Glycine (Gly) and proline (Pro) residues often occur in β-turns, particularly on the surface of globular proteins.

Examples of β-Pleated Sheet Structures:

•Most immunoglobulins have a β-pleated conformation.
•Some enzymes, like hexokinase, contain a mixed α-β conformation.
c) Tertiary Structure:
• The tertiary structure refers to the 3D, folded, and biologically active conformation of a protein.
• This structure reflects the overall shape of the protein molecule.
Stabilization:
• The 3D tertiary structure is stabilized by interactions between side-chain functional groups.
• These interactions include:
• Covalent disulfide bonds
• Hydrogen bonds
• Salt bridges (ion pairs)
• Hydrophobic interactions
•Hydrogen Bonding in Tertiary Structure:
• The side chains of tryptophan and arginine can act as both hydrogen bond donors and acceptors.
• Other amino acids such as lysine, aspartic acid, glutamic acid, tyrosine, and histidine can also serve as
both donors and acceptors in forming ion pairs (salt bridges).
•Salt Bridges:
• A salt bridge can form between two oppositely charged amino acids, such as:
• Glutamate: With a γ-carboxyl group.
• Lysine: With an ε-amino group.
• These salt bridges are typically found on the surface of proteins.
d) Quaternary Structure:
• Refers to a complex or assembly of two or more separate peptide chains.
• These peptide chains are held together by non-covalent interactions or, in some cases, covalent
interactions.
•Types of Quaternary Structure:
• Homogeneous Quaternary Structure: If the subunits are identical.
• Heterogeneous Quaternary Structure: If the subunits are different.
•Examples:
• Insulin: Composed of two different chains, A and B, forming a heterogeneous quaternary structure.
• Hemoglobin: Contains four chains, two α chains and two β chains, forming a heterogeneous quaternary
structure.
•Polymers in Quaternary Structure:
• These complexes can be classified based on the number of subunits, such as:
• Dimers: Two subunits.
• Trimers: Three subunits.
• Tetramers: Four subunits.