SSCG 1112

Proteins and Amino Acid

Functional Categories (Part 2)
 Lecture Outline

 Diverse Functions of Protein

 Classification of Protein (Based on shape)
 Structure-Function Relationship
 Levels of Protein Structure (Interactions
and bonds)
DIVERSE FUNCTIONS OF
PROTEINS
 Catalysis
 Structure
 Movement
 Defense
 Regulation
 Transport
 Storage
 Stress response
 Functions of Protein
Proteins have most diverse functions amongst all
biomolecules:

1) Catalysis
 All enzymes are protein. Not all proteins are enzyme.
 They accelerate biochemical reaction involved in metabolism.
 Perform it activity under mild condition of pH and temperature.
2) Structure
 Provide protection and support.
 Collagen: component of connective tissue.
 Fibroin: silk protein (provide significant mechanical strength).
 Elastin: in tissues of blood vessels and skin.
3) Movement
 Involved in all cell movements.
 E.g. Actin, tubulin and cytoskeletal protein (in cell division,
endocytosis, exocytosis, amoeboid movement).
4) Defense
 Fibrinogen and thrombin: blood clotting protein; prevent blood loss
when wounded.
 Antibodies: produced by lymphocytes; protect from bacterial
infection.
5) Regulation
 Insulin and glucagons: peptide hormones to regulate blood glucose
level.
 Growth hormone.
 Growth factors (peptide) such as PDGF (Platelet-Derived Growth
Factor) and EGF (Epidermal Growth Factor).
6) Transport
 Hemoglobin: carries O2 to tissues from lungs.
 Lipopeptides LDL and HDL: transport lipid from liver and intestines
to organs.
 Ceruloplasmin: serum protein that transport iron and copper.
7) Storage
Ovalbumin: in bird eggs and casein; in mammalian milk.

8) Stress response
Cytochrome P450: convert variety of toxic organic contaminant to
less toxic derivatives.
Metallothionein: cysteine-rich; to sequestering toxic metal.
Heat shock protein (HSP): promote correct refolding of damaged
protein or its degradation when severely damaged.
CLASSIFICATION OF PROTEIN
(BASED ON SHAPE)

insoluble in water soluble in water

Fibrous protein
 Secondary structure (either α-helices or β-pleated sheets)
forms the dominant structure.
 Often have regular repeating structures.
 Insoluble in water.
 Long, rod-shaped molecule.
 High physical strength – suitable for structural,
protective and movement function.
 E.g. Keratin in skin, hair, nails, muscles and collagen.
Globular protein
 Highly diverse group of proteins.
 Soluble and form compact spheroidal molecules in water.
 Have tertiary structure and some have
quaternary structure.
 Consist of relatively straight runs of secondary structure
joined by stretches of polypeptides that abruptly change
direction.
 Catalysis , Defense, Regulation. Transport, Stress response
 E.g. Enzymes, immunoglobulin, albumin (fatty acid
carrier in blood), hemoglobin.
STRUCTURE-FUNCTION
RELATIONSHIP
 Unique 3-D conformation (native structure)
 Interaction and chemical bonds
 Denaturation of protein
 Structure and Function
 Protein consist of linked long chain amino acids. Have >50 amino acid
residues.
 Amino acids linked by peptide bonds.
 Proteins have amino-end and carboxyl-end.
 20 amino acids (compare to our 26 alphabets!)
 There are many possible ways to arrange the residues in 3-D space, but
only one UNIQUE is used by each protein.
 This is called its unique 3D native conformation.
 Exist in many conformations:
 Primary structure
 Secondary structure
 Tertiary structure
 Quaternary structure
 Primary Structure
 Primary structure of a protein DETERMINES the other levels
of structure.

 A single amino acid substitution:

 Substitution of amino acids can cause from negligible effect
to complete loss of activity (glutamine to valine).
 Can give rise to a malfunctioning protein (E.g. sickle-cell
anemia).
 In sickle cell anemia, red blood cells cannot bind oxygen
efficiently.
 Red blood cells have a characteristic of sickle shape.
 Sickle cell trapped in blood vessels, cutting off circulation and
cause organ damage.
 Secondary Structure
 A local spatial arrangement of the backbone atoms without
the side chains (R).
 Secondary structure is the initial folding pattern (periodic
repeats) of the linear polypeptide.
 Hydrogen bonds form between amino (N-H group) to the
carbonyl group (COO-) of amino acid 4 residues away.
 2 main types of secondary structure:
 α-helix
 β-pleated sheet
 Structure of both types are stabilized by hydrogen bonds
between carbonyl (COO-) and amino (N-H group).
 Secondary Structure
Some amino acids do not foster -helical formation.
Examples:
1. Glycine – the R group is too small (H), this cause
polypeptide chain too flexible.
2. Proline – contain rigid ring that prevents rotation of N-C
bond. It has no N-H group available to form hydrogen
bond that is crucial in -helix structure.
3. Charged amino acids (E.g. glutamate and aspartate) and
amino acid with large R group (E.g. tryptophan) not
suitable with -helix structure.
 α-helix
 The α-helix is parallel right-handed or clock-wise.
 Each turn has 3.6 a.a residues.
 The helix is stabilized by H-bonds between –N-H
and –C=O groups of every 4th amino acid.
 α-helices can wind around each other to
form‘coiled coils’ that are extremely stable and
found in fibrous structural proteins such as keratin,
myosin (muscle fibers) etc.
 R group lie outward from the α-helix.
α -helix
 ß-sheet
 Extended stretches of 5 or more a.a are called β-strands.
 β-strands organized next to each other make β-sheets.
 Parallel β-sheet: adjacent strands are oriented in the same
direction, (N-end to C-end).
 Antiparallel β-sheet: adjacent strands run opposite to each
other.
 There can also be mixed β-sheets.
 H-bonding pattern varies depending on type of sheet.
 β-sheets are usually twisted rather than flat.
 R group lie outward from the β-sheets.
Parallel
Polypeptide chains are arranged in the same
direction.
Antiparallel
Polypeptide chains are organised in opposite direction.
More stable than parallel -pleated sheet due to the fully
collinear hydrogen bond.
 Tertiary Structure
 3D arrangement of the entire polypeptide chain INCLUDING
the side chains (R).
 The conformations of the side chains and positions of any
prosthetic groups are part of the tertiary structure.
 Non-polar residues are buried inside, polar residues are
exposed outwards to aqueous environment.
 Many proteins are organized into multiple‘domains’.
 Domains are compact globular units that are connected by
a flexible segment of the polypeptide.
 Each domain is contributes a specific function to the overall
protein
 A protein domain: will invariably have more than 1 element
of 2° structure (>1 α helix or β strand), as well as
connecting units (E.g. they will have more than just α-
helices or β-strands).
 5 kinds of bonds stabilize tertiary structure:
 H-bonds
 van der Waals interactions
 Hydrophobic interactions
 Ionic interactions
 Disulphide linkages
 In disulphide linkages, the S-H groups of two neighboring
cysteins form a –S-S- bond called as a disulphide linkage. It
is a covalent bond, but readily cleaved by reducing agents.
 Quaternary Structure
 Association of 2 or more subunits in 3-D space.
 Consist of more than one polypeptide chains.
 Each polypeptide chain is called a subunit.
 Subunits (monomers) can be identical or different.
 The protein is homopolymeric or heteropolymeric.
 Disulfide bonds usually stabilize the oligomer.