This document provides an overview of protein chemistry, structure, and function. It begins by listing learning objectives related to describing protein structures like the peptide bond and classifying proteins. It then covers the primary, secondary, tertiary, and quaternary structures of proteins. Examples of globular proteins like hemoglobin and myoglobin and fibrous proteins like collagen and elastin are described. The document also discusses protein folding, misfolding diseases, and classification of proteins by function.

1. CHEMISTRY OF
PROTEINS
 Learning Objectives
 As a result of this class, students shall be able to: Describe the
peptide bond
 Describe the Biuret qualitative and quantitative tests for
proteins
 Classify proteins as simple or conjugated
 Classify proteins based on their functions
 Classify proteins based on their shapes
 Describe the primary, secondary, tertiary and quaternary
structures of proteins
 Describe protein denaturation
 Discuss protein misfolding; Prion diseases, Alzheimer disease

2. Learning Objectives,
continued
 Describe myoglobin and hemoglobin as examples of
globular proteins
 Describe collagen and elastin as examples of fibrous
proteins
 Describe the following hemoglobinopathies in simple
terms—sickle cell disease, HbC, HbSC, Thalassemias
 Compare collagen with elastin in terms of structure
and functions. Describe the collagen and elastin
diseases
 Differentiate between plasma and serum.
 Identify the serum proteins and their functions

3.  STRUCTURE
 FUNCTIONAL CLASSIFICATION
 FIBROUS PROTEINS
 GLOBULAR PROTEINS

4.  20 amino acids are
used to synthesize
proteins; they are
joined together by
peptide bonds.
 Linear sequence of
the amino acid
residues contains the
information
necessary to
generate a protein
molecule with a
unique three-
dimensional shape.
 Complexity of
protein structure
is best analyzed
by considering
the molecule in
terms of 4
organizational
levels: primary,
secondary,
tertiary, and
quaternary
levels.

5. Primary Structure of
Proteins
 The primary structure of a protein is
defined as the linear sequence of its
amino acids.
 Understanding the primary structure of
proteins is important because many
genetic diseases result in proteins with
abnormal amino acid sequences, which
can cause improper folding and loss or
impairment of normal function.

7.  Peptide bonds join
the individual amino
acids, attaching the
α-amino group of one
amino acid to the α-
carboxyl group of
another.
 The peptide bonds
can be hydrolyzed
non-enzymatically by
prolonged exposure
to a strong acid or
base at elevated
temperatures.
 Peptide bonds have a
partial double-bond
character (shorter
than single bonds;
rigid and planar).
 They are generally in
the trans
configuration.
 They are polar, and
can hydrogen bond
to each other or to
other polar
compounds.

8.  Amino-terminal (N-
terminal) end:
written to the left.
 Carboxyl-terminal
(C-terminal) end:
written to the
right.
 Each component
amino acid in a
polypeptide is
called a “residue”
or “moiety”.
 --Amino acid sequences are
read from the N- to the C-
terminal end of the peptide.

9. SECONDARY STRUCTURE
OF PROTEINS
 The secondary structure of a protein is
generally defined as regular arrangements
of amino acids that are located near to each
other in the linear sequence.
 Examples of such elements are the α-helix,
β-sheet, and β-bends (reverse turns).
 Some secondary structure is not regular,
but rather is considered non-repetitive
(loop or coil).

10. A and B are antiparallel: the two strands are in
opposite orientations.
B and C are parallel: the two strands are in the same
orientation

11. Diagrams 2 and 3 show two different views of the same
beta - pleated sheets rich protein. In yellow, the parts of
the protein involved in the beta - pleated sheets; in
pink, some alpha - helices. Loops are in grey / white.

12.  Secondary structural elements are stabilized by
extensive hydrogen bonding.
 Supersecondary structures (motifs) are produced by
packing side chains from adjacent secondary
structural elements close to each other.

13. TERTIARY STRUCTURE OF
GLOBULAR PROTEINS
--The primary structure of a
polypeptide determines its
tertiary structure.
--Domains are the fundamental
functional and three-
dimensional structural units
of a polypeptide.
--They are formed from
combinations of motifs.
--Tertiary structure refers to
the folding of the domains
and their final arrangement
in the polypeptide.
Tertiary structure is stabilized by
disulfide bonds, hydrophobic
interactions, hydrogen bonds,
and ionic bonds.
A specialized group of proteins,
named chaperones, is required
for the proper folding of many
species of proteins.

14. QUATERNARY STRUCTURE
OF PROTEINS
 Proteins consisting of
more than one
polypeptide chain have
quaternary structure.
 2 subunits—dimeric (the
protein is a dimer);
 3 subunits—trimeric;
 4 subunits—tetrameric;
 Several subunits—
multimeric.
 --Subunits are held
together by noncovalent
interactions (e.g.,
hydrogen bonds, ionic
bonds, and hydrophobic
interactions).

15.  In some proteins, the subunits function
independently of each other.
 In other proteins, e.g., hemoglobin, the subunits
work cooperatively: the binding of oxygen to one
subunit of hemoglobin increases the affinity of the
other subunits for oxygen.

16. DENATURATION OF
PROTEINS
 Proteins can be denatured: unfolded and
disorganized; denaturation makes them
nonfunctional.
 --denaturation results in the unfolding and
disorganization of the protein’s secondary and
tertiary structures;
 --not accompanied by hydrolysis of peptide bonds
(primary structure not affected).
 Denaturation agents include heat, organic solvents,
mechanical mixing, strong acids or bases, detergents,
and ions of heavy metals such as lead and mercury.

17. PROTEIN MISFOLDING
 Protein misfolding may occur
spontaneously, or
 caused by genetic mutation.
 Some apparently normal proteins can,
after abnormal proteolytic cleavage,
take on a unique conformational state
that leads to the formation of long,
fibrillar protein assemblies consisting of
β-pleated sheets.
 The spontaneously aggregating proteins
are called amyloids.

18. Alzheimer’s disease
 Protein misfolding is implicated
in Alzheimer's disease (AD) --a
neurodegenerative disorder.
 AD is characterized by
accumulation of amyloid plaque
(Aβ) and neurofibrillary tangles
(abnormal form of tau protein).

19. Prion diseases
 Definition of Prion: A microscopic protein particle
similar to a virus but lacking nucleic acid---- the
infectious agent responsible for scrapie and certain
other degenerative diseases of the nervous system.
 Prions — short for proteinaceous infectious particle
— are infectious protein structures that replicate
through conversion of normal host proteins of the
same type.

20.  Though the exact mechanisms of
their actions and reproduction are
unknown, it is commonly accepted
that prions are responsible for a
number of previously known but
little-understood diseases generally
classified under transmissible
spongiform encephalopathy diseases
(TSEs), including scrapie (a disease
of sheep), kuru (found in members of
the cannibalistic Foré tribe in Papua
New Guinea), Creutzfeldt-Jakob
disease (CJD), Chronic Wasting
Disease, Fatal Familial Insomnia
(FFI), Gerstmann-Sträussler-
Scheinker syndrome (GSS), and
bovine spongiform encephalopathy
(BSE or mad cow disease).
 These diseases
affect the
structure of
brain tissue and
all are fatal and
untreatable.
 So far all prions
discovered are
believed to
infect and
replicate by
propagation of
an amyloid
fold.

21. FUNCTIONAL CLASSIFICATION
OF PROTEINS
 Proteins can be classified
according to their
biological functions as
follows:
 1. Enzymes: They are
proteins that catalyze
almost all the chemical
reactions in the cells.
E.g., catalase,
glucokinase, hexokinase.
 2. Contractile and motile
proteins: They give the
cells and organisms the
ability to contract, to
change shape, or to move
about. Examples are the
muscle proteins myosin,
actin, troponin,
tropomyosin .
 3. Structural proteins: They
serve as supporting filaments,
cables, or sheets, to give
strength and protection to
biological structures.
Examples are collagen,
keratin, and elastin.
 4. Transport proteins:
Transport proteins of the
blood bind and carry specific
molecules or ions from one
organ to another. E.g.,
hemoglobin and plasma
proteins.
 Transport proteins of cell
membranes transport
nutrients/ions across the
membrane into and out of
cells. E.g., Na+/K+-ATPase.

22.  5. Defence proteins:
These include the
antibodies which
recognize and destroy
invading bacteria, viruses,
or foreign proteins;
 the blood-clotting proteins
(e.g., fibrinogen and
thrombin) which prevent
loss of blood when the
vascular system is injured,
the snake venoms,
bacterial toxins, and toxic
plant proteins (e.g., ricin)
which function in
defence.
 6. Nutrient and storage
proteins: These include
the proteins in the seeds
of many plants, e.g.,
gliadins and glutelins of
cereals, and legumin of
legumes.
 The major protein of egg
is ovalbumin and casein is
the major protein of milk.
 Ferritin of animal tissues
stores iron.

23.  7. Regulatory proteins: These proteins regulate
cellular or physiological activities.
 They include protein hormones such as insulin and
glucagon, and the gene-regulating proteins, such as
histones and non-histone proteins.

24. Globular and Fibrous
proteins
 Proteins can also be
classified as either
globular or fibrous,
based on their overall
shape.

25. Fibrous proteins
 Fibrous proteins are elongated
molecules in which the secondary
structure (either α-helices or β-pleated
sheets) forms the dominant structure.
 Fibrous proteins are insoluble, and play
a structural or supportive role in the
body, and are also involved in
movement (as in muscle and ciliary
proteins).
 One feature of fibrous tissues is that
they often have regular repeating
structures.

26.  Keratin, for example, which is found in hair, horns,
wool, nails, and feathers, is a helix of helices (2 pairs
of α-helices wound around one another).
 Collagen is the major protein component of
connective tissue. In collagen, every third amino acid
is glycine and many of the others are proline.

27. Globular proteins
 Globular proteins are a highly diverse group of
proteins that are soluble and form compact
spheroidal molecules in water.
 All have tertiary structure and some have
quaternary structure in addition to secondary
structure.
 Globular proteins typically consist of relatively
straight runs of secondary structure joined by
stretches of polypeptides that abruptly change
direction.
 Enzymes are globular proteins as are transport
proteins and receptor proteins.
 Myoglobin and hemoglobin are globular proteins.

28.  Aside from the difference in shape (elongated vs.
spheroidal) and solubility (insoluble vs. soluble),
fibrous proteins generally have only primary and
secondary structure whereas globular proteins have
tertiary and sometimes quaternary structure in
addition to primary and secondary structure.

29. COLLAGEN
 Collagen: the most
abundant protein in the
human body.
 A typical collagen
molecule is a long, stiff,
extracellular structure in
which three polypeptides
(referred to as “α-
chains”, each 1000 amino
acids in length) are wound
around one another in a
rope-like triple-helix.
 The chains are held
together by hydrogen
bonds.

30. Collagen Diseases
 Collagen diseases
include Ehlers-Danlos
syndrome,
Osteogenesis
imperfecta, Alport
syndrome and
Epidermolysis bullosa.

31. Ehlers-Danlos syndrome

32. Osteogenesis imperfecta

33. ELASTIN
Elastin consists of fibers, whose main
property is their elasticity. Elastin
fibers are composed of protein
molecules with the following properties
that differ from collagen in many
respects.
Elastin contains:
 --Abundant glycine, about 33% (as in
collagen)
 --Little hydroxyproline
 --No hydroxylysine

34.  Abundant hydrophobic amino acids
 --Helical segments that are responsible for its
elasticity
 --Desmosine in non-helical segments, which is
responsible for cross-linkage of the molecules to form
a network that can alter its configuration when
stretched.

35. The diagrams illustrate the cross-linking of elastin to
form a network
(a) in the relaxed state;
(b) when stretched.

36. ELASTIN DISEASES
 Elastin diseases include cutis laxa, Marfan’s syndrome
(mutation in fibrillin gene) and α1-antiproteinase (α1-
antitrypsin) deficiency----causing emphysema.

37. Alpha-1 antitrypsin
deficiency and
emphysema Cutis laxa

38. HEMOGLOBIN AND MYOGLOBIN (EXAMPLES OF
GLOBULAR PROTEINS)
 Myoglobin (Mb) is a
hemeprotein present in
heart and skeletal
muscle.
 It functions both as a
reservoir for oxygen,
and as an oxygen carrier
that increases the rate
of transport of oxygen
within the muscle cell.
 ---consists of a single
polypeptide chain that is
structurally similar to
the individual subunit
polypeptide chains of
the hemoglobin
molecule.

39.  Myoglobin has 153
aminoacyl residues
and molecular
weight of 17,000.
 The surface is polar
and the interior
nonpolar—this is
characteristic of
globular proteins.
 Apart from two
histidine residues
that function in
oxygen binding, the
interior of myoglobin
contains only
nonpolar residues
(e.g., Leu, Val, Phe,
Met).

40. HEMOGLOBIN

41. Hemoglobin types in adult
human blood
HbA α2β2 90%
HbF α2γ2 <2%
HbA2 α2δ2 2-5%
HbA1c α2β2-glucose 3-9%

42. Binding of oxygen to
myoglobin and hemoglobin

43. Hemoglobin diseases
(hemoglobinopathies)
 They include:
 Sickle-cell (HbS) disease
 HbC disease
 HbSC disease
 Thalassemias
 Methemoglobinemias