Fundamentals of

Protein Structure
Dr. Saba Abdi
Assistant professor
Depatrment Of Biochemistry
King Saud University
 Proteins play key roles in a living
system
examples of protein functions

Transport:
Some proteins transports various
substances, such as oxygen, ions, and Alcohol
so on. dehydrogenas
e oxidizes
alcohols to
Information transfer: aldehydes or
For example, hormones. ketones
Catalysis:
Almost all chemical reactions in a
living cell are catalyzed by protein Haemoglobin
enzymes. carries
oxygen
Physical cell support and shape (tubulin,
actin, collagen)
Mechanical movement (flagella, mitosis,
muscles) Insulin
controls the
amount of
sugar in the
blood
 Protein classification
Classification based of structure:
1.Globular Proteins:
Usually water soluble, compact, roughly
spherical
Hydrophobic interior, hydrophilic surface

Globular proteins include enzymes,carrier

and regulatory proteins
 Protein classification
Classification based of structure:
2. Fibrous Protein:
Provide mechanical support

Often assembled into large cables or threads

-Keratins: major components of hair and nails

Collagen: major component of tendons, skin,

bones and teeth
 Protein classification
Classification based of composition:
1.Simple proteins: albumin, lysozyme

1.Conjugated proteins: haemoglobin,

myoglobin, cytochromes,
immunoglobins.
 Properties of proteins
Molecular weights range from 10000-several hundred
thousand
Generally proteins are soluble in water, except the
membrane proteins which are hydrophobic
Absorb light in the UV range. Maximum absorption at 280nm
due to aromatic a.a
Have a specific Isoelectric pH [pI]. Positively charged below
PI, and negatively charged above pI

Proteins are charged molecules, but the charge depend on

the pH of the buffer.
Move under an electric field and can be separated by
electrophoresis
Give color reactions; e.g blue color with Ninhydrin reagent.
 Amino acid: Basic unit of
protein

R
Different side
- chains, R,
NH3 +
C COO determin the
Amino group Carboxylic
acid group properties of 20
H amino acids.
An amino
acid
 20 Amino acids
Glycine Alanine (A) Valine Isoleucine (I) Leucine (L)
(G) (V)

Proline (P) Methionine (M) Phenylalanine (F) Tryptophan (W) Asparagine

(N)

Glutamine (Q) Serine Threonine (T) Tyrosine (Y) Cysteine (C)

(S)

Asparatic acid (D)Glutamic acid (E) Lysine (K) Arginine (R) Histidine (H)

White: Hydrophobic, Green: Hydrophilic, Red: Acidic, Blue: Basic

 zwitterions
Under normal cellular conditions amino
acids are zwitterions (dipolar ions):
Amino group = -NH3+
Carboxyl group = -COO-
Proteins are linear polymers
of amino acids
R1 R2
NH3 C COO NH3 C COO

H H A carboxylic acid
H2 O condenses with an
H2 O
amino group with the
R1 R2 R3 release of a water

NH3 C CO NH C CO NH C CO

H Peptide H Peptide H
bond bond
The amino acid
F T D sequence is called
A G N S K A
G S as primary structure
 Peptide bond
Peptide bond - linkage between amino
acids is a secondary amide bond
Formed by condensation of the -carboxyl
of one amino acid with the -amino of
another amino acid (loss of H2O molecule)
Primary structure - linear sequence of
amino acids in a polypeptide or protein
 Planar peptide groups in a
polypeptide chain
Rotation around C-N bond is restricted
due to the double-bond nature of the
resonance hybrid form
Peptide groups (blue planes) are
therefore planar
Trans and cis conformations
of a peptide group
Nearly all peptide groups in proteins are
in the trans conformation
 Amino acid sequence is
encoded by DNA base
sequence in a gene
DNA DNA base
molecule G C sequence
C G
G C
C G
T
T
A
A
A T
A T
G C
C G
G C
C G

Each Protein has a unique
structure

Amino acid
sequence
NLKTEWPELVGKSV
EEAKKVILQDKPEAQ
IIVLPVGTIVTMEYRI
DRVRLFVDKLDNIAE
VPRVG
Folding!
 Hierarchical nature of
protein structure
Primary structure (Amino acid sequence)

Secondary structure -helix, -sheet

Tertiary structure Three-dimensional structure
formed by assembly of secondary structures

Quaternary structure Structure formed by
more than one polypeptide chains
 Basic structural units of
proteins: Secondary structure
-helix -sheet

Secondary structures, -
helix and -sheet, have
regular hydrogen-
bonding patterns.
 -helix
-helix:(is composed of one
polypeptide chain)
It is 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 in order to avoid
interfering sterically with each other.
 -helix
Right handed -helix is stabilized by intra-chain
hydrogen bond.
Counting from the N-terminal end, the C=O group
of each amino acid residue is hydrogen bonded to
the N-H group of the amino acid four residues
away from it in the covalently bonded sequence.
(each C ) of one a.a. is hydrogen bonded to the (-
NH) of the next fourth amino acid in the chain (1
4).
There are 3.6 residuesfor each turn of the helix.
The pitch (complete turn distance) is 0.54 nm (5.4
A0).
The -helix
 Examples of -helix

Some proteins are entirely -helix eg

-keratin fibrous protein in hair.
Other proteins have different
amount of -helix e.g. hemoglobin
has 80% -helix
Some proteins have no -helices eg
keratin in silk
 -pleated sheet
The surface of -sheet appear pleated and these structures are
called -pleated sheet
-sheet are composed of two or more separate peptide chains.
(-strands) or segments of polypeptide chains that are almost
fully extended.
The peptide backbone is almost completely extended.
It is stabilized by:
Interchain hydrogen bonds(between the polypeptide
backbone of separate polypeptide chains)(It is formed between
(-NH) group of one chain or one segment and (C=O) of the
adjacent chain (or segment)
Intrachain hydrogen bonds(between the polypeptide
backbone of single polypeptide chain folding back on itself)
There are two types of -pleated sheet:Parallel -sheet
Antiparallel -sheet
-pleated sheet
 Three-dimensional
structure of proteins

Tertiary
structure
Quaternary
 TertairyStructure
It is spatial arrangement of amino acids that are far
apart in the linear sequence.
The polypeptide chain is folded in three of dimension.
Bonds responsible for its stability:
(1)Hydrogen bonds (between side chains)
(2)Hydrophobic bonds (between the non-polar side
chain of a.a.)
(3)Electrostatic bonds (salt bonds)(Formed between
oppositely charged group in the side chains of amino
acids)e.g. epsilon-amino group of lysine and carboxyl
group of aspartate, interact electrostatically to stabilize
the protein structure.
 Quarternary Structure
This structure for proteins that have more than one polypeptide
chains.
Refers to the organization of subunits in a protein with multiple
subunits (an oligomer)
Subunits (may be identical or different) have a defined
stoichiometry and arrangement
Subunits are held together by many weak, noncovalent interactions
(hydrophobic, electrostatic)
The interaction between subunits are stabilized by:
hydrogen bonds
electrostatic bonds
hydrophobic bonds
e.g. of proteins having quaternary structure:Insulin (2 subunits),
Lactate dehydrogenase enzyme: (4 subunits), hemoglobin (4
subunits)
 Close relationship between
protein structure and its
function
Example of enzyme Hormone receptor Antibody
reaction
substrate
s
enzym A enzym
BCH 221 Enzymology
e e

Final Examination
B
Matching
Digestion
the shape
of A!
to A enzym
e
A

Binding to A