A comprehensive presentation on Four levels of protein structure for MBBS, BDS, B Pharm & Biotechnology students to facilitate self- study.

1. Four levels of protein structure
Dr. Rohini C Sane

2. Structure of proteins
❖ Proteins are polymers of amino acids and made up of one or more
polypeptide chains .
❖ Every protein in its native state has a unique three dimensional
structure which is referred to as its conformation.
❖The number and sequence of these amino acids in the protein are
different in different proteins.
❖The function of a protein arises from its conformation.
❖Protein structure can be classified into four levels of organization.

3. Configuration and Conformation of a molecule
Configuration of
compound
denotes the spatial
relationship between
particular atoms
e.g. L- amino acids
and D-amino acids
Conformation of
molecule
means the spatial
relationship of every
atom in a molecule
e.g. rotation of a
portion of the
molecule

4. Four levels of protein structure
Proteins are the polymers of L--amino acids. The structure of proteins is rather complex
which can be divided into four levels of organization.
Proteins: polypeptide with more than 50 amino acid residues

5. Four levels of structural organization of proteins
❖ Proteins are polymers of amino acids and made up of one or more
polypeptide chains .
❖Four levels of structural organization can be recognized in proteins:
1. Primary structure: is determined by the number and sequence of amino
acids in the protein.
2. Secondary Structures: is the conformation of polypeptide chain formed
by twisting or folding . It occurs when amino acids are linked by hydrogen
bonds to form -helix and -sheets .
3. Tertiary Structure : is the three dimensional arrangement of protein
structure. It is formed when alpha-helices and beta-sheets are held
together by weak interactions.
4. Quaternary structure: occurs in protein(oligomers) consisting of more
than one polypeptide chain where certain polypeptides aggregate to
form one functional protein.

6. Four orders of protein Structure
 Primary structure is determined
by the sequence of amino acids.
Secondary Structures: the
number and sequence of amino
acids in the protein. It occur
when amino acids are linked by
hydrogen bonds to form -helix
and -sheets .
 Tertiary Structure : is the three-
dimensional arrangement of protein
structure.
Quaternarystructure:occursinprotein(oligomers)
consistingofmorethanonepolypeptidechainwherecertain
polypeptidesaggregatetoformonefunctionalprotein.

7. Four
orders of
protein
structure:
Bricks
Wall
Rooms
Building
Amino acids 
(Bricks )
Secondary structure
(bends /twist in walls)
Tertiarystructure(self–containedroom)
Primary structure
(walls)
Quaternarystructure(buildingwithsimilar/dissimilarrooms
Structural Hierarchy
of proteins

8. Structural hierarchy of proteins
• Primary structure : is a linear sequence of amino acids forming a backbone of
proteins .It refers to the order in which amino acids are linked together in the
peptide chain. e.g. Glutathione: Tripeptide : Glutamic acid-Cysteine-Glycine
Methionine Enkephalins : pentapeptide: Try- Gly- Gly- Phe -Met
• (N-terminal end) → H2N - - COOH (C-terminal end)
• Peptide bond → linear , planner ,rigid ,partial double bond character
❖Secondary Structures :spatial arrangement of proteins by twisting of
polypeptide chain= folding patterns in proteins (alpha-helix ,beta-sheet )
❖Tertiary Structure : Three dimensional structure generated by interaction
between the amino acid residues of functional proteins.
❖Quaternary structure : refers to the spatial arrangement of subunits of
proteins which are joined by non-covalent interactions . This is seen in proteins
with two or more polypeptides chains(oligomers).
❖Super secondary Structures :indicate folding patterns in proteins

9. Primary structure of proteins
• Primary structure of proteins denotes the number and sequence of amino acids in protein.
The successive amino acids are linked by peptide bond(covalent bond).
• Generally ,amino acids are arranged as a linear chain . Each component amino acid is
called a residue or moiety. Very rarely, proteins may be a branched form or circular form
(Gramicidin) . Primarystructureofproteinsislargelyresponsibleforitsfunctions.
• The branching points in the polypeptide chain may be produced by interchain disulphide
bridges (the covalent disulphide bonds between different polypeptide chains in the same
protein) or portion of the same polypeptide chain (intrachain). They are part of primary
structure.
• Eachpolypeptidewillhaveanaminoterminal(N-terminal)withfreeaminogroupandacarboxyterminal
ends(C-terminal)withfreecarboxygroup.By convention, they are represented with amino
terminal on the left and carboxy terminal end on the right end.
• The amino acids composition of protein determines its physical and chemical properties.
• Primarystructureofproteins(sequenceofaminoacids)isdeterminedbythegenescontainedinDNA.
Primarystructureofnumberofproteinsareknowntoday.e.g.Insulin, Glucagon,Ribonuclease,Growth
hormones.AnychangeinthePrimarystructureofproteinsaffecttheirfunctions.

10. Peptide bond formation
• Formation of peptide bond = a
covalent bond is formed by amide
linkage between the - carboxyl
group of one amino acid and -
amino group of another amino acid
by removal of a water molecule.
• Successive amino acids are
joined/cemented by peptide bond
( -CO-NH) in proteins .
➢The peptide bonds form strong
backbone of polypeptide and side
chains of amino acid residue project
outside the peptide backbone.
Dipeptide :two amino acids and one peptide bond ( not two bonds)

11. Characteristics of Primary structure of proteins:1
1. Apeptidecontains twoormoreaminoacidresiduesjoinedtogetherbyapeptidebonds.Individualamino
acidscanbeconsideredasbricks.
2. Formationofpeptidebond=acovalentbondisformedbyamidelinkagebetweenthe-aminogroupof
oneaminoacidand-carboxylgroupofanotheraminoacidbyremovalofawatermolecule.
3. CharacteristicsofaPeptidebond:
a. Rigid,covalent,stable,strongandcanbehydrolyzed bytheactionofproteolyticenzymes,acidsand
alkalis
b. Planerandwithpartialdoublebond(nofreedomofrotation)incharacter
c. –C=O,NH–Existintrans-configuration.Bothgroupsarepolarandinvolvedinhydrogenbonds.
d. Impartstabilitytotheprimarystructureofproteins(disulphidebondsarealsoresponsibleforthestability)
e. Thesidechainarefreetorotateoneithersideofthepeptidebond.
f. Distancebetweenaminoacidsis1.32Awhichismidwaybetweenthatofsinglebond(1.49A)and
doublebond(1.27A)
g. Ramachandranangles:areangleofrotation→determinethespatialorientationofpeptidechain

12. Characteristics of Primary structure of proteins:2
5. In polypeptide chain , at one end there will be one free alpha amino group→ N-
terminal end and protein biosynthesis starts from amino terminal end (the first
amino acid ).
6. The other end of polypeptide chain , is carboxy terminal end (the last amino acid)
where there is free alpha carboxy group.
7. All other alpha-amino acids and alpha-carboxy groups are involved in peptide bond
formation.
8. Writing of peptide structures –by convention ,the amino acid sequence is written
from left to right with the free amino end (N- terminal acid/residue→ number 1 by
tradition) on left and ending with the free carboxyl end (C –terminal amino acid /
residue).
9. Shorthand to read peptides : three letter or one letter abbreviation/ short hand
form of amino acids in protein to be read from N-terminal residue on left of
peptide e.g. (Gly-Ala–Val)→Glycyl –Alanyl –Valine → G A V
Or NH2-Gly-Ala-Val-COOH
10. Naming peptides : for naming peptides the amino acid Suffixes ine (Glycine → to
glycyl) , an (Tryptophan), ate ( Glutamate→ Glutamyl) by yl with the exception of C-
terminal amino acid.

13. Use of symbols in representing a peptide
• A tripeptide → 3 amino acids and 2 peptide bonds is shown.
H3 N + Glutamate – Cysteine –Glycine -COO-
E – C – G
Glu – Cys – Gly
Glutamyl – cysteinyl –Glycine
• Free amino end (N- terminal acid/residue) →-N + H3 is on the left.
Free carboxyl end (C –terminal amino acid / residue)→ -COO- is on right .
• The amino acid sequence is written and read from left to right. This is the
chemical shorthand to write proteins.
one letter abbreviation
three letter abbreviation
 Peptide name
 Amino acids in a peptide

14. Polypeptide chain showing N-terminal and C-terminal
• Schematic diagram
NH3
+ – CH – CO –NH –CH – CO –NH –CH – CO –NH –CH – CO –NH- CH – COO-
I I I I I
R1 R2 R3 R4 R5
N- terminal peptide bond amino acid residue C - terminal
N C

15. Amino acid Amino acid
composition
ofHuman
Cytochrome C
(104AA)
Amino acid
compositionof
Bovine
Chymotrypsinogen
(245AA)
Ala 6 22
Arg 2 4
Asn 5 15
Asp 3 8
Cys 2 10
Glu 8 5
Gln 2 10
Gly 13 23
His 3 2
Ile 8 10
Amino acid Amino acid
compositionof
Human
Cytochrome C
(104AA)
Amino acid
compositionof
Bovine
chymotrypsinogen
(245AA)
Leu 6 19
Lys 18 14
Met 3 2
Phe 3 6
Pro 4 9
Ser 2 28
Thr 7 23
Trp 1 8
Tyr 5 4
Val 3 23

16. Clinical applications of primary structure
❖Clinical applications of primary structure :
1. Presence of specific amino acid at a specific position/number is very
significant for a particular function of protein . Any change in the
sequence is abnormal and may affect the functions and properties
of proteins .
2. Many genetic diseases result from protein with abnormal amino
acid sequences. If the primary structure of the normal and
mutated proteins are known ,the this information may be used to
diagnose or clinical study of the disease.

17. Secondary structure of proteins
3 dimensional Conformation of the
polypeptide chain by twisting or
folding is referred to as a secondary
structure.
(Types :Alpha-helix ,Beta-pleated sheet)

18. Secondary Structures of proteins
• Secondary Structures :spatial arrangement of proteins by twisting of
polypeptide chain= folding /helical coiling patterns in proteins (alpha- helix)
or zig-zag linear( beta-sheet) or mixed form by hydrogen bonding and
disulphide bonds .
• Secondary Structures denotes the steric relationship of amino acids close to
each other.
• One of the form of coiling of the polypeptide chain is right handed alpha-
helix.
• Since proteins are made up of L-amino acids , the coiling of polypeptide
chain into right handed alpha-helix is facilitated.
• Super secondary Structures :indicate folding patterns in proteins
• Linus Pauling (Noble 1954)and Robert Corey (Noble 1951) proposed alpha-
helix and beta-pleated sheet structures of polypeptide chains.

19. Primary and Secondary structure of Human Insulin
Carboxy-terminalend
A chain : Asparagine
B chain : Threonine
Amino-terminal end
A chain : Glycine
B chain : Phenylalanine
A polypeptide chain :
21 amino acids
B polypeptide chain :
30 amino acids
intrachain disulphide bond : between
Cysteine residues( 6 th amino acid of A
chain with 11 th amino acid of B chain)
interchain disulphide bonds 



 

20. Different kinds of secondary structures
❖Different kinds of secondary structures:
1. Alpha-helix (helicoid state)
2. Beta-pleated sheet (stretched state)
3. Loop regions
4. Beta-bends or beta-turns
5. Disordered regions
6. Triple helix

21. Alpha()-helix
• Alpha()-helix : is called Alpha() because the first structure elucidated by
Linus Pauling (Noble 1954)and Robert Corey (Noble 1951).It is most common
spatial structure of protein .
• If a backbone of polypeptide chain is twisted by equal amounts about each 
-carbon , it forms a coil or helix . The -helix is a rod like structure .
• These hydrogen bonds have an essentially optimal nitrogen to oxygen (N-O)
distance of 2.8 A. Thus, carbonyl(CO)group of each amino acid is hydrogen
bonded to the -NH of the amino acid that is situated 4 residues ahead in a
linear sequence .
• The axial distance between adjacent amino acids is 1.5 A and gives 3.6
amino acid residues per turn of helix.

22. Characteristics of Alpha-helix (a type of Secondary structure of proteins):1
❖Characteristics of Alpha-helix :
1. The most common stable conformation formed spontaneously with the lowest energy.
2. right or left handed Spiral/helical /tightly coiled structure in the stable form. A right
handed helix turns in the direction that the fingers of right hand curl when its thumb
points in the direction the helix rises.
3. Stabilized by Hydrogen bonds (weak, strong enough due to large number to stabilize
alpha helix structure) of the main chain which forms the back bone. Side chains of amino
acids extend outwards from the central axis.
4. Hydrogen bonding occurs between the carboxyl oxygen of one peptide bond and the
amide nitrogen of another peptide bond and 3 amino acid residues apart / further down
in the chain (e.g. 5th is hydrogen bonded to 9th and 6th is bonded 10th and so on). All
peptide bonds except the first and the last in polypeptide chain participate in hydrogen
bonding.
5. Each peptide bond in the polypeptide chain participates in intrachain hydrogen bonding.

23. Characteristics of Alpha-helix (a type of Secondary structure of proteins):2
6. Each turn of Alpha-helix :
a. contains 3.6 amino acids residues /turn of the helix with the R group protruding outward
radially.
b. A rise along the central axis of 1.5A per residue and travels distance of 5.4 nm/turn.
c. Spacing of each amino acid residue ( axial distance between amino acids) is 0.15nm (1.5
A translation).
6. The right handed -helix more stable and common than left handed helix. Left handed
helix are rare because of presence of L-amino acid found in protein which exclude left
handedness).
7. Proline , hydroxy proline and Glycine disrupt alpha-helix formation and introduce a kink
or a bend in the helix.
8. Large number of acidic (Asp,Glu) or basic amino acids (Lys , Arg ,His)or amino acid with
bulky R group disrupt Alpha-helix.
9. Abundant in Myoglobin , Hemoglobin , Keratin of hair (-Keratin ), proteins in wool and
virtually, absent in Chymotrypsin.

24. Right and left-handed alpha-helix structure in protein molecule
• A Right-handed alpha-helix turns in
direction that fingers of right hand
curl when thumb points in direction
of helix rises.
• A left- handed alpha-helix turns in
direction that fingers of left hand curl
when thumb points in direction of
helix rises.

25. Schematic diagram of alpha-helical structure of proteins
Alpha-helix :EachoxygenofC=Ogroupofapeptidebondformsahydrogenbondwiththehydrogenatom
attachedtothenitrogeninapeptidebond,fouraminoacidsfurtheralongthepolypeptidechain.
Each turn of Alpha-
helix travels
distance of 5.4
nm/turn.
Alpha-helix

26. Alpha-helix (a type of Secondary structure of proteins):3
Alpha-helix:Hydrogenbondingoccursbetweenthecarboxyloxygenofonepeptidebondandtheamide
nitrogenof another peptidebondand3aminoacidresiduesapart/furtherdowninthechain(e.g. 5th is
hydrogenbondedto9th and6th isbonded10th andsoon).Allpeptidebondsexceptthefirstandthelastin
polypeptidechainparticipateinhydrogenbonding.

27. Schematic diagram of alpha-helical structure of proteins
Alpha-helix:StabilizedbyHydrogenbonds(weak,strongenoughduetolargenumbertostabilizealpha-helix
structure)ofthemainchainwhichformsthebackbone.Sidechainsofaminoacidsextendoutwardsfrom
thecentralaxis.
Sidechainsofaminoacidsextend
outwardsfromthecentralaxis.
StabilizedbyHydrogen
bonds

28. Examples of proteins with alpha-helical structure
❖Alpha-helical structure occur in both fibrous and globular proteins.
Fibrous proteins with alpha-helical
structure
Globular proteins with alpha-helical
structure
-Keratin of hair , nail , skin Hemoglobin (80%)
Fibrin of blood Myoglobin
Myosin and Tropomyosin of muscle
Proteins in wool
Digestive enzyme→ Chymotrypsin is virtually devoid of alpha- helix in its
structure.

29. Formation of hydrogen bond in alpha()-helix
NH3
+ – CH – CO –NH –CH – CO –NH –CH – CO –NH –CH – CO –NH- CH – COO-
I I I I I
R1 R2 R3 R4 R5
---------Hydrogen bond ( N-O distance =2.8 A)-------------
3.6 amino acid residues

30. Helix destabilizing amino acids
❖Helix destabilizing (helix beakers)amino acids : Glycine , Proline
❖Proline as a helix beaker : since nitrogen of Proline residue in a peptide
linkage has no substituted hydrogen (as it has imino NH-group instead of
amino group) for the formation of hydrogen bond with other residue , Proline
fits only the first turn of an alpha-helix. Elsewhere, it produces bend and turn.
❖Glycine as a helix beaker : all bends in alpha-helix are not caused by Proline
residue but bend often occurs also at Glycine residues as side chain of Glycine
is small.

31. Peptide bond formation with Proline
Schematic diagram
H H
NH2 – C – CO N C – COOH → NH2 –CH – CO – C – COOH +
I I
R1 R1
Amino acid Proline peptide nitrogen of Proline has no substituted hydrogen

32. Structural importance of Alpha-helix
❖Structural importance of alpha-helix : Several alpha-helices can coil
around one another like a twisted twined cable forming strong stiff
bundles of fibers and give mechanical support.

33. Characteristics of Beta-pleated sheet (Secondary structure of proteins)
❖Characteristics of Beta-pleated sheet :where proposed/described by Linus Pauling (Noble
1954)and Robert Corey (Noble 1951). It is Beta because , it was the second type of structure
after alpha-helix they elucidated.
1. When alpha-helix of keratin is stretched the hydrogen bonds are broken and new
hydrogen bonds are formed between -CO and NH- of adjacent parallel chain / neighboring
polypeptide segments giving rise to an arrangement of the backbone of protein
molecule→ Beta-pleated sheet. (Beta-sheet appear pleated).
2. is stabilized by the hydrogen bonds .
3. Hydrogen bonding occurs between two polypeptide chains(H-bonds are intrachain) or
two regions (neighboring segments) of a single chain of polypeptide chain (H-bonds are
interchain).
4. Composed of 2 or more segments of fully extended polypeptide chains.
5. Two polypeptide chains in a beta-pleated sheet may run in the same direction (parallel
beta-pleated sheets ) with regard to amino and carboxy terminal ends of polypeptide
chain or in the opposite directions (anti-parallel beta-pleated sheets).
6. Distance between adjacent amino acid residue is 3.5 A(translation).
7. Major structural motif in fibroin of silk (anti-parallel), flavodoxin (parallel), Carbonic
anhydrase(both) ,some regions of globular proteins like chymotrypsin, ribonuclease.

34. Intrachain hydrogen bonds (within single polypeptide chain) and interchain
hydrogen bonds (between two or more polypeptide chains )
Interchainhydrogen bonds:areformedbetweenamidehydrogen( NH)ofonepolypeptidechain
andcarbonyl(C=O)ofneighboringpolypeptidechain.
Intrachainhydrogen bonds:areformedbetweenamidehydrogen( NH)ofonepolypeptidechain
andcarbonyl(C=O)ofthesamepolypeptidechain.

35. ComparisonofAlpha-helix and Beta-pleated sheet: secondary
structure of proteins
Criteria Alpha-helix Beta-pleated sheet
Structure Coiledrodlike Fullyextendedsheetlike
Axialdistancebetweenaminoacids 1.5A 3.5A
Numberofconstituentpolypeptidechain One Oneormorepolypeptide
chains
Stabilizedbyhydrogenbondsbetween
NHandC=Ogroupsin
thesame
polypeptidechain
Different/thesame
polypeptidechain
hydrogenbondsare Parallelto
polypeptide
backbone
Perpendicularto
polypeptidebackbone

36. ComparisonofAlpha-helixandBeta-pleatedsheet:secondarystructuresofproteins
hydrogenbondsarePerpendicularto
polypeptidebackbone.
hydrogenbondsareParallel
topolypeptidebackbone
Coiledrodlike Fullyextendedsheetlike
Axialdistancebetween
aminoacids 1.5A
Axialdistancebetweenaminoacids3.5A
Oneconstituentpolypeptide
chain
Alpha-helix Beta-pleated sheet
Oneormoreconstituentpolypeptidechain

37. Alpha-helix ,Beta-pleated sheet :secondary structures of important proteins
Alpha-helix : abundant in Myoglobin , hemoglobin , Keratin of hair (- Keratin), proteins in wool and absent
in chymotrypsin
Beta-pleated sheet : fibroin of silk ,some regions of globular proteins like chymotrypsin, ribonuclease

38. Thearrangementofpolypeptidechainsinbeta-pleatedsheetconformation
❖The arrangement of polypeptide chains in beta- pleated sheet conformation
can occur two ways:
1. Parallel beta- pleated sheet
2. Anti-parallel beta- pleated sheet
➢A beta- sheet can also be formed by either a single polypeptide chain folding
back on to itself (H-bonds are intrachain and stabilized by intramolecular
hydrogen bonding ) or separate polypeptide chains (H-bonds are interchain) .
➢As such , the -helix and -sheet are commonly found in the same protein
structure . In the globular proteins , -sheet form the core structure.

39. Intrachain hydrogen bonds (within single polypeptide chain) and interchain
hydrogen bonds (between two or more polypeptide chains )
Interchainhydrogen bonds:areformedbetweenamidehydrogen( NH)ofonepolypeptidechain
andcarbonyl(C=O)ofneighboringpolypeptidechain
Intrachainhydrogen bonds:areformedbetweenamidehydrogen( NH)ofonepolypeptidechain
andcarbonyl(C=O)ofthesamepolypeptidechain

40. Hydrogen bonds in beta-pleated sheet structure
H O H
N C N
C N C
O H O
C N C
O
I II I
II II
II
II
I
I
•
•
•
•
H O
•
•N
HI
N
I
H
•
C
Hydrogen bond between chains
Beta-pleated sheets(or simply  sheets )are composed of two or more segments of fully
extended peptide chains.
Schematic diagram

41. Parallel and anti-parallel beta- pleated sheet
Parallel beta- pleated
sheet :same direction of N
& C- terminal ends of
peptide/Two polypeptide
chains run in the same
directions (parallel).
Anti-parallel beta-pleated
sheet: Opposite direction
of N & C- terminal ends
peptide/ Two polypeptide
chains run in the opposite
directions (antiparallel).

42. Structure of beta-pleated sheet
N-terminal C–terminal
N-terminal C-terminal
C-terminal N-terminal
The polypeptide chains in the beta() –sheets may be arranged either in parallel
(the same direction) or anti-parallel (opposite direction).
Parallel beta- pleated sheets
Antiparallel beta- pleated sheets

43. Properties of Beta-pleated sheet (Secondary structure of proteins)
Parallel beta- pleated sheet: the polypeptide are side by side and lie in same direction of N
& C-terminal ends of peptide, so that their terminal residues are at the same end ( N-terminal
faces to N-terminal ). It is stabilized by intrachain hydrogen bonds.
Anti-parallel beta- pleated sheet : Opposite direction of N & C-terminal ends peptide.

44. Anti-parallel beta-pleated
sheet: the polypeptide lie in
opposite directions i.e. N –
terminal end of one
polypeptide is next to C –
terminal of the other. (N-
terminal faces C-terminal
end of peptide- Anti- parallel
directions ).
It is stabilized by interchain
hydrogen bonds.
Anti parallel pleated beta-sheet of Secondary structure of proteins

45. Clinical application of beta-pleated sheet : Secondary structure of proteins
❖Clinical application of beta- pleated sheet : Secondary structure of proteins
found in both fibrous and globular proteins.
• Anti-parallel beta-sheets conformation is less common in human proteins.
❖Occurrence of beta-sheet :
1. Silk fibroin(the best example in nature)
2. Amyloid in human tissue: a protein that accumulates in Amyloidosis and
Alzheimer’s disease .Dementia occurring in middle age associated with this
Amyloidosis .

46. Loop regions and their Importance
❖Loop regions :
• About half of the residues in a typical globular protein are present in alpha-
helices or beta-sheet . Remaining residues are present in loop or coil
conformation. Loop regions though irregularly ordered (lacking regular
secondary structure) are biologically important as they are more ordered
secondary structure.
• Loop or coiled  the random coils (disordered and biological unimportant
conformation of denatured proteins).
❖Importance of loop regions : form the antigen-binding sites of antibodies.

47. Beta-bend or beta-turn and its Importance
❖Beta-bend or beta-turn or hairpin turn or reverse turn : refers to the segment , in
which a polypeptide chain abruptly reverses direction and often connects the ends
of the adjacent antiparallel beta-strands hence they are named as beta-turn.
Globular proteins contain Beta-bends.
❖Characteristics of beta-bend(-bend) :
1. consists of four successive amino acid residues.
2. Frequently contains Proline or Glycine or both.
3. is stabilized by Intrachain disulphide bridges and hydrogen bonds (hydrogen bond
is formed between the first amino acid to the forth in the bend).
4. occur primarily at protein surfaces and impart globular shape (rather than
linearity) to proteins.
5. Promote the formation of anti-parallel beta –pleated sheets .
6. Importance of beta-bends : they help in the formation of compact globular
structure.

48. Beta bends & non –repetitive secondary structure of proteins
Beta-bends may be formed in many proteins by the abrupt U-turn folding of the chain.
Intrachain disulphide bridges and hydrogen bonds stabilize these bends .

49. Disordered region and its Importance
• Not all residues are necessarily present or ordered secondary
structure.
• Specific residues of many proteins exist in numerous conformation in
solution and thus they are called Disordered regions.
• Many Disordered region become ordered region when a specific
ligand is bound .
• e.g. The stabilization of Disordered regions of the catalytic sites of
many enzymes when ligand is bound .
• Importance of Disordered region : gives flexibility and performs a
vital biological role.

50. Disordered region of enzyme and its Importance
Schematic diagram
Many Disordered region become ordered region when a specific ligand is bound .
Disordered region gives flexibility and performs a vital biological role.
Disordered regions of
enzyme- catalytic site
ordered regions of
enzyme
Substrate added to
enzyme catalyzed
reaction mixture
Enzyme with
Disordered regions
set free at the end of
reaction
Product
Enzyme-substrate complex –induced fit
+

51. Super secondary structures of proteins
❖A protein molecule may contain all types of arrangements in different parts .
Thus , a part may form an -helix to be followed by -pleated sheets which
may include parallel or anti- parallel regions with intervening  turns ,loop
regions and disordered regions. Such combinations of secondary structural
features are called Super secondary structures.
➢These grouping of certain secondary structural elements of proteins occur
in many unrelated globular proteins.

52. Characteristic properties of Super secondary structures of proteins
❖Characteristic properties of Super secondary structures of proteins:
1. Folding patterns involving - helices, -pleated sheets (which may be parallel or
anti- parallel regions with intervening  turns) ,loop regions and disordered
regions.
2. - - 2 : in this structure ,an -helix connects two parallel strands of -pleated
sheets. It is the most common motif.
3. -hairpin : consists of antiparallel  -sheets joined by relatively tight reverse
turn/ short loops.
4.  motif: two successive anti-parallel helices packed against each other with
their axis inclined.
5. -barrel: extended -pleated sheets role up to form three different types of
barrels
6. Globular proteins like Chymotrypsin , Myoglobin and Ribonuclease have Super
secondary structures instead of uniform secondary structures.
7. The secondary and Super secondary structures of large proteins are recognized
as domains or motifs.

53. Domains of the globular proteins
❖Domains of the globular protein :
➢The term domain is used to represent the basic structural and functional units of
protein with tertiary structure(denotes a compact globular functional unit of
protein).
➢Relatively independent region and may represent a functional unit.
➢ are usually connected with relatively flexible areas of protein (e.g. immunoglobulin)
❖3 Domains of Phenylalanine hydroxylase :
a. Catalytic
b. Regulatory
c. Protein-protein interaction domain
❖Calmodulin : a calcium binding regulatory protein(regulates intracellular calcium
levels )
❖A polypeptide with 200 amino acids normally consists of two or more domains.

54. - - 2 Protein motifs
- - 2 : an -helix connects two
parallel strands of -pleated sheets.
Folding patterns involving -
helices and -pleated sheets.

55.  motif and -hairpin Protein motifs(Super secondary structure of proteins)
 motif: two successive anti-parallel
helices packed against each other with their
axis inclined.
-hairpin : consists of antiparallel  -sheets joined
by relatively tight reverse turn/ short loops.



56. -barrel Protein motifs(Super secondary structure of proteins)
-barrel: extended -pleated sheets role
up to form different types of barrels
Role of Super secondary structure of
membrane proteins

57. -barrels located across Mitochondrial outer membrane
-barrels located across the Mitochondrial outer membrane facilitate transport of moieties
associated with functions of mitochondrion (e.g. Biological oxidation , Urea cycle etc. ).

58. Protein motifs(Super secondary structure of proteins)

59. Predominant Specific structural motifs of common proteins
Protein Predominant Specific structural motifs present
Myoglobin Alpha-helix and beta-pleated sheets
Flavodoxin Parallel beta-pleated sheets
Super oxide dismutase Anti-parallel beta-pleated sheets
Fibroin of silk anti-parallel beta-pleated sheets
Carbonic anhydrase Both Parallel and Anti-parallel beta-pleated
sheets
Keratin Alpha-helix →Coiled coil
Collagen Triple-helix
Elastin No specific motif

60. Approximateamountofaalpha-helixandbeta-structureinsome singlechainprotein
Protein Total residue Alpha-helix
(residue%)
Beta-structure
(residue%)
Myoglobin 153 78 0
Cytochrome C 104 39 0
Lysozyme 129 40 12
Ribonuclease 124 26 35
Chymotrypsin 247 14 45
Carboxy peptidase 307 38 17
Data from C. R. Cantor and P.R. Schimnel ,Biophysical chemistry , the conformation of biological macromolecules p 100 1980

61. Tertiary Structure of proteins
Tertiary Structure :
Three dimensional structure
generated by interaction between
the amino acid residues of functional
proteins.

62. Tertiary Structure of proteins
❖Tertiary structure of globular proteins defines the steric relationship of amino
acids which are far apart from each other in the linear sequence but are close in
three dimensional aspects i.e. Three-dimensional structure of globular proteins is
dependent on the primary structure.
• It is a compact structure with hydrophobic side chains held interior while
hydrophilic groups are on the surface of the protein molecule. This arrangement
ensures stability of the molecules.
• Three-dimensional structural conformation of globular proteins provides and
maintains the functional characteristics.
• Functions of globular proteins are maintained because of their ability to recognize
and interact with a variety of molecules .
• This structure reflects the overall shape of the molecule.
• Primarystructureofproteinisfoldedtoformcompact,biologicallystableandactive
conformation i.e. a three-dimensional globularprotein. It is referred as its Tertiary
structure.
• e.g. Insulin ,Myoglobin

63. Tertiary structure of Human Insulin
In1953,FrederickSanger determinedprimarystructureofInsulin(apancreaticproteinhormone)and
showed forthefirsttimethataproteinhasapreciselydefinedaminoacidsequence(primarystructure).
PrimarystructureofHumanInsulinisfoldedtoformcompact,biologicallystableandactiveconformation
i.e. a three-dimensionalglobularprotein.It is referred as its Tertiary structure.

64. Tertiary Structure of Myoglobin(Mb)
Myoglobin:PrimarystructuresimilartosinglemonomericunitofHemoglobin withasinglepolypeptidechainhaving
153aminoacids(molecularweight16700).It haseightalpha–helices(AtoH)andonehemegroup(ironcontaining
porphyrin)tofacilitateitsfunctionofoxygenstorageincardiacandskeletalmusclesinhumanbody,WhalesandSeals.

65. Tertiary Structure of Hemoglobin (Hb)
Hemoglobin:Tetramericwith4hemegroups.Eachpolypeptidechainhassimilarstructureto single
polypeptidechainofMyoglobin.Ithasaloweraffinity foroxygenthanMyoglobin.Foursubunits of Hb
functioncooperatively.TetramericstructureofhemoglobinfacilitatessaturationwithO2inthelungand
releaseofoxygenasittravelsthroughthecapillarybed.

66. Covalentbondsstabilizing proteinstructure
❖Proteins are stabilized by three types of covalent bonds:
1. Peptide bonds
2. Disulphide bonds
3. Lysinonorleucine bonds

67. Peptide bonds : Covalentbondsstabilizing proteinstructure
• Formation of peptide bond = a
covalent bond is formed by amide
linkage between the - carboxyl
group of one amino acid and -
amino group of another amino acid
by removal of a water molecule.
• Successive amino acids are
joined/cemented by peptide bonds
( -CO-NH) in proteins .
➢The peptide bonds form strong
backbone of polypeptide and side
chains of amino acid residue project
outside the peptide backbone.
Dipeptide :two amino acids and one peptide bond ( not two bonds)

68. Lysinonorleucine bonds: Covalent bonds responsible for protein structure
❖Lysinonorleucine bonds:
• A bond formed between oxidized lysine residue with unmodified lysine side
chain to form a crosslink, both within and between the triple helix units.
e.g. Collagen
• Cross links confer tensile strength to the protein .

69. Structure of collagen Type 1
❖ Structure of collagen Type 1:
1. Triple-stranded helical structure present throughout the collagen
molecule
2. Shape : rod-like molecule → 1.4 nm diameter and 300 nm length
3. Number of Amino acid residues : 1000 per for each polypeptide
chain (3000 /molecule)
4. Amino acid contribution : 1/3 rd of amino acids are Glycine (every
third amino acid in collagen is Glycine.
5. Repetitive amino acid sequence : (Gly – X –Y )n ,where X and Y
represent other amino acids
6. Proline and hydroxyproline : 100 per for each polypeptide chain
7. Function of Proline and hydroxyproline : confer rigidity to the
collagen molecule
8. Collagen Fibril formation : Triple helical molecule of collagen
assemble to form elongated fibrils . It occurs by a quarter staggered
alignment i.e. each triple helix is displaced longitudinally from its
neighbor collagen molecule by about one-quarter of its length
9. Collagen Fiber formation : Collagen Fibrils assemble to form rod like
fibers .
10. Strength of Collagen Fiber : contributed by covalent cross linking of
formed between Lysine and hydroxylysine and also between Proline
and hydroxyproline.

70. Disulfide bonds : Covalentbondsstabilizing proteinstructure
❖Proteins are stabilized by three types of covalent bonds (peptide bonds ,
disulphide bonds and Lysinonorleucine bonds).
• Cysteine : with functional group -SH (sulfhydryl)
• Cystine : functional group -S-S-(disulphide)
• A covalent disulfide (-S-S)bond formed between the sulfhydryl group (-SH)of two
Cysteine residues in the same or different polypeptide chains.
• Intra chain S-S bond →Cysteine at 6th position linked to that at 11th position of A
chain of Insulin
❖Inter chain S-S bonds :
(1)Cysteine at 20th position of A chain is linked to that at 19th position of B chain of
Insulin
(2) Cysteine at 7th position of A chain is linked to that at 7th position of B chain of
Insulin
➢These disulfide bonds contribute to structural conformation and stability of
proteins . Performic acid cleaves the disulfide bonds between polypeptide units.

71. Role of Cysteine and Cystine in formation Covalentbondsstabilizing proteinstructure
Cystine has disulfide (S-S) as a functional group . It is formed from Cystine
(Dicysteine)after oxidation. Cystine on reduction yields two Cysteine molecules.
Two Cysteine residues can connect two polypeptide chains by formation of
Interchain disulfide bonds or links . e.g. Keratin , Insulin

72. Intrachain and Interchain Disulfide bonds (S-S bonds) in Human Insulin
Carboxy-terminalend
A chain : Asparagine
B chain : Threonine
Amino-terminal end
A chain : Glycine
B chain : Phenylalanine
A polypeptide chain :
21 amino acids
B polypeptide chain :
30 amino acids
intrachain disulphide bond : between
Cysteine residues( 6 th amino acid of A
chain with 11 th amino acid of B chain)
interchain disulphide bonds 



 

73. ClassificationAlpha-keratinstructurebasedonSulphuranddisulphidebridgescontent
Type of keratin abundant in
structure
Sulphur and disulphide bridges content
Hard keratin Hair, nails ,horn High Sulphur and disulphide bridges (rich
in cysteine residue) content
Soft keratin Skin Low Sulphur and disulphide bridges (poor
in cysteine residue) content
➢ Disulphide bonds are common in structural proteins like Keratin ,
extracellular enzymes such as ribonuclease but rare in Intracellular globular
proteins.
➢ These bonds help to stabilize protein molecules against denaturation and
confer additional stability them .

74. Importance of Disulphide bonds of Keratin structure in hair
• Springiness of hair is due to the characteristic coiled coil structural motif.
• When stretched , the coiled coil will untwist and resume the original
structure.
• Hair styling /dressing : Stretching of hair using moist heat to break
disulphide bonds of keratin structure.
• Epidermolysis bullosa : abnormalities in keratin structure →loss of integrity
of skin
Hair styling Hair dressing / status of disulphide bond of keratin
Stretching hair styling Reduction of disulphide bonds of keratin to break these bonds
Curling hair styling Re-oxidation of disulphide bonds of keratin to form new bonds

75. Hair styling /dressing : Stretching of hair using moist heat to break disulphide
bonds of keratin structure
Hard keratin and Soft keratin Stretching hair styling: Reduction of
disulphide bonds of keratin to break
these bonds
High Sulphur and disulphide bridges
(rich in cysteine residue) content

76.  and -conformation of Keratin in Hair waving
Hair with -helices of -Keratin
-helices of -Keratin stretched → conformation of Keratin
 conformation of Keratin reverted to -helices of -Keratin
cooling
exposed to moist heat

77. Biochemical aspects of Hair curling(waving)
Hair to be curled is bent to appropriate shape
Disulfide bonds of Cystine are converted to sulfhydryl groups of Cysteine
Uncoiling of -helical structure of -Keratin
New Disulfide bonds are formed between Cysteine residues of keratin→ altered -helical
structure of -Keratin
Hair with desired curls (temporary structure)
Growth of new hair with native conformation without curls
Application of reducing agents
Removal of reducing agents and addition of oxidizing agent
Hair washed and cooled

78. Alteration of Keratin structure in hair waving
I I I I I
S S S S S
I I I I I
S S S S S
I I I I I
I I I I I
SH SH SH SH SH
SH SH SH SH SH
I I I I I

SH

SH

SH

SH

SH
SH

SH

SH
 SH

SH
S
S
S
S S
S
S
SSH
SH
S
S
Reduction
Curling
Oxidation
S
S
Schematic diagram

79. Hair styling /dressing
Hair curling(waving) Hair straitening

80. Non-covalent interactions in Tertiary structure of globular proteins
❖ Tertiary structure of globular proteins : refers to the three-dimensional conformation of
proteins generated and maintained by weak bonds(valence forces) / non-covalent
interactions such as:
a. Hydrogen bonds : formed between -CO and NH- of two different peptide bonds or -OH
group of hydroxy amino acids(Serine etc.) and-COOH groups of acidic amino acids
Aspartic or Glutamic acid.
b. Ionic bonds/electrostatic interactions/salt bridges : formed between oppositely charged
groups when they are in close vicinity . They are also formed oppositely charged R groups
of polar amino acid residues . e.g. basic (Histidine, Arginine , Lysine)and acidic amino
acids (Aspartic acid, Glutamic acid)
c. Hydrophilic interactions : water loving groups are associated with water.
d. Hydrophobic interactions : formed between hydrophobic groups (hydrocarbon like)of
amino acids like Alanine and Phenylalanine.
e. Van der Waal forces : weak ,but collectively contribute maximum towards the protein
structure.
➢During folding of globular proteins (spherical/round), hydrophobic groups prefer to be
interior and Hydrophilic groups prefer to be on the surface of protein molecule.
➢The tertiary structure acquired by a native protein is always thermodynamically most
stable.

81. Properties of Hydrogen bonds responsible for protein structure
❖Properties of Hydrogen bonds responsible for protein structure:
• Hydrogen bonds are formed between NH- and –CO groups of peptide bonds
by sharing single hydrogen .
• Each Hydrogen bond is weak but collectively they are strong. A large number
of Hydrogen bonds significantly contribute stability to the protein structure.
• Hydrogen bonds may be intrachain( between same polypeptide chain) or
interchain( between different polypeptide chains)
• Side chains of 11 out of 20 standard amino acids can participate in hydrogen
bonding (i.e. Tryptophan, Tyrosine , Aspartic acid, Asparagine ,Glutamic acid,
Glutamine , Histidine , Arginine , Serine , Threonine, Lysine).
• Formation of Hydrogen bonds between polar side groups on the surface of
protein enhances solubility of the protein.

82. Structure of interchain Hydrogen bonds
H O H
I II I Schematic diagram
N C N
C N C
II I II
O H O
H H O
C I N C
II N C N
O II I
O H
interchain Hydrogen bond
III

83. Hydrogen donor and Hydrogen acceptor in Hydrogen bonds
responsible for protein structure
❖Hydrogen bonds responsible for protein structure : are weak electrostatic
interactions between one electronegative atom like O or N and hydrogen
atom linked to second electronegative atom .
Group of Hydrogen donor Hydrogen donor
-NH Imidazole , indole ,peptide
-OH Serine ,Threonine
Group of Hydrogen acceptor Hydrogen acceptor
COO- Aspartic acid ,Glutamic acid
C=O Peptide
-S-S- Disulphide

84. Hydrophobic bonds responsible for protein structure
❖Hydrophobic bonds in protein structure :
➢are formed by interactions between Hydrophobic R groups(non-polar side
chains) of neutral amino acids like Alanine , Valine , Leucine, Isoleucine,
Methionine, Phenylalanine , Tryptophan by eliminating water molecules.
➢are not true bonds.
➢ serves to hold lipophilic side chains together.
➢The occurrence of hydrophobic forces is observed in aqueous environment
wherein the molecules are forced to stay together.

85. Hydrophobic interactions
I
I
I
NH-CH-CO
HC-CH3
CH2
CH3
H3C CH3
CH
CH2
NH-CH-CO
I
I
Leucine
Isoleucine
Hydrophobic interactions:
1. non-polar side chains of neutral
amino acids tend to be closely
associated with each other in
protein confirmation.
2. are Not true bonds.
3. Observed in aqueous
environment wherein the
molecules are forced to stay
together.
Schematic diagram

86. Electrostatic bonds: Bondsresponsibleforproteinstructure
Electrostatic /ionic / salt bonds/salt bridges : formed between oppositely charged
groups when they are in close vicinity i.e. negatively charged group linked to positively
charged group of amino acid e.g. COO ⁻ of Glutamic acid associates with NH₃⁺of
Lysine. They are also formed oppositely charged R groups of polar amino acid residues.
Positive charges contributed by : epsilon amino group of lysine , guanidium group of Arginine,
imidazole group of Histidine
Negative charges contributed by : beta and gamma carboxyl group of Aspartic acid and
Glutamic acid respectively

87. Electrostatic interactions
NH-CH-CO
CH
C
O O-
N+ H3
(CH2)4
NH-CH2-CO
Schematic diagram
Aspartate: acidic amino acid
Lysine: basicaminoacid
❖Electrostatic interactions:
are formed between
negatively charged groups
( e.g. COO -) of acidic amino
acid with positively charged
groups (e.g. -N+H3) of basic
amino acid .
❖They are also formed
oppositely charged R
groups of polar amino acid
residues.
Electrostatic interactions →
I
I
I
I

88. Van Der Waals forces: Bondsresponsibleforproteinstructure
❖Van Der Waals forces/interactions : Electrically neutral molecules associate by
electrostatic interactions due to induce dipoles.
❖Characteristics of Van Der Waals forces/interactions :
• are the non-covalent associations.
• are very weak ,but collectively contribute maximum towards the protein
structure.
• act only on short distances.
• include both an attractive and repulsive component between both polar and
non-polar side chain of amino acid residues.

89. Van Der Waals forces : Bondsresponsibleforproteinstructure
Van Der Waals forces/interactions : Electrically neutral molecules associate by
electrostatic interactions due to induce dipoles. These are the non-covalent associations.
They are very weak ,but collectively contribute maximum towards the protein structure.
They act only on short distances. They include both an attractive and repulsive component
between both polar and non-polar side chain of amino acid residues.
induce dipole

90. Factors stabilizing the tertiary structure of Globular proteins
A B C D C=O S N
O- H

E F G H N
+
H3 S O
Ionic interactions
Covalent Cysteine interlinks

Association of hydrophobic R groups within molecule,
shielded from water

Hydrogen bonds
Schematic diagram

91. Weak bonds stabilizing Tertiary structure of proteins
Peptide bond Serine Lysine Alanine Phenylalanine Cysteine
NH CH2OH N+H3 CH3 S
O O-
O C=O C=O CH3 S
C
Peptide bond Asp Asp Alanine Phenylalanine Cysteine
Hydrogen bonds ionic bond hydrophobic interactions disulfide bond
=
Tertiarystructureofanativeproteindenotesoverallarrangementandinter-relationshipofvariousregionsor
domainsofsinglepolypeptidechain.Itisthermodynamicallythemoststableconformation.
Schematic diagram

92. Domains of globular proteins
❖Domains of globular protein :
➢The term domain is used to represent the basic structural and functional units of
protein with tertiary structure( denotes a compact globular functional unit of
protein).
➢Relatively independent region and may represent a functional unit.
➢ are usually connected with relatively flexible areas of protein (e.g. immunoglobulin)
❖3 Domains of Phenylalanine hydroxylase :
a. Catalytic
b. Regulatory
c. Protein-protein interaction domain
❖Calmodulin : a calcium binding regulatory protein(regulates intracellular calcium
levels )
❖A polypeptide with 200 amino acids normally consists of two or more domains.

93. Domains of globular proteinsimmunoglobulinsandPhenylalaninehydroxylase
Domainsofimmunoglobulinsareusually
connectedwithrelativelyflexibleareasofprotein.
3DomainsofPhenylalaninehydroxylase:Catalytic,
Regulatory,Protein-proteininteractiondomain

94. Domains of Calmodulin : a calcium binding regulatory protein
Domains of
Calmodulin

95. Domains of ribonuclease
Domains of ribonuclease :catalytic and RNA binding domain to facilitate its function of
cleavage of ribonucleic acids(RNA)

96. Quaternary structure of globular proteins :
refers to the spatial arrangement of
subunits (polypeptide chains) linked by non-
covalent interactions in protein molecule .

97. Quaternary structure of globular proteins:1
❖A number of proteins are made up of with two or more peptide chains(subunits/
monomers / protomers )which may be identical or unrelated. Such proteins are
termed as oligomers. Subunits of oligomers are not covalently linked(non-covalent
forces). This association of subunits to form protein molecule is known as
Quaternary structure. Not all proteins are polymeric.
✓Globular proteins loose their functions on dissociation of subunits.
❖Forces involved to aggregate subunits :
a. Hydrogen bonds
b. Ionic /electrostatic interactions
c. Hydrophobic interactions
d. Van der Waal forces
➢The same weak bonds are involved in secondary and tertiary structure in this
associations.

98. Quaternary structure of globular proteins:2
❖Quaternary structure of globular proteins :refers to the spatial arrangement of
subunits (polypeptide chains) linked by non-covalent interactions in three
dimensional complexes. It occurs in proteins with two or more peptide chains. .
❖Monomer or promoter or subunits :Individual polypeptide chain of oligomeric
protein
• Monomers in Quaternary structure of globular proteins stabilized by
a. Hydrogen bonds
b. Hydrophobic interactions non-covalent bonds
c. Ionic bonds /electrostatic interactions/salt bridges
d. Van der Waals forces
❖Dimer : 2 polypeptide chains (e.g. Insulin)
❖Tetramers : 4 polypeptide chains (e.g. LDH ,Hemoglobin ,SGOT)
❖Oligomers : proteins with 2 or more polypeptides chain

99. Examples of proteins(oligomers) having quaternary structure
❖Examples of proteins having quaternary structure :
• Hemoglobin
• Creatine kinase
• Alkaline phosphatase
• Glycolytic enzymes :
a. Aldolase
b. Lactate dehydrogenase
c. Pyruvate dehydrogenase

100. Types of globular protein based on number of constituent polypeptide chains
Type Component polypeptide chains as functional unit Exampleofglobularprotein
Dimer 2 polypeptide chains Creatine kinase (CK)
Homodimer contains 2 copies of the same polypeptide chain
→2 Alpha() chains +2 Beta( )chains
Hemoglobin
Heterodimer contains 2 different types the polypeptides as a
functional unit →with A and B polypeptide chains
Insulin
Tetramer 4 polypeptide chains ( H and M type polypeptide
chains 2 each )
Lactate dehydrogenase
(LDH)
Tetramer 4 polypeptide chains ( light and heavy chains
polypeptide chains 2 each )
Immunoglobulin G

101. Quaternary structure of Hemoglobin
Hemoglobin (HbA1)has
4 Polypeptides chains
(tetramer) associated by
non-covalent bonds :
2 Alpha() chains
+
2 Beta( )chains
It possesses Quaternary
structure(oligomeric).
Inthis, Rgroupcontactsare
presentbetweensimilarside
chainsandthereisverylittle
contactbetweendissimilar
side chains.
HbA:
Tetramer
22
Eachchainhasoneheme
groupandsooneFe2+ ion

102. Importance of Quaternary structure of globular proteins
❖Importance of Quaternary structure of globular proteins :
1. Subunits of oligomeric proteins may either function independently of each
other or may work cooperatively as in Hemoglobin where the binding of
oxygen to one subunit of tetramer increases the affinity of other subunits
for oxygen.
2. Oligomeric proteins are regulators of cell metabolism & cellular functions.

103. Deoxy –Hb Hb O₂ Hb O₄ Hb O₆ Hb O₈
T form ↓ ↓ ↓ ↓ ↓
↑
R form
Oxygenation of Hemoglobin
Quaternary structure of Hemoglobin favors its functions :Binding of oxygen(O2) to
one heme unit facilitates oxygen binding by other subunits.

104. Four levels of structural organization of proteins
Theoverallconformationofaprotein,theparticularpositionoftheaminoacidchainsinthreedimensional
spacedeterminesthefunction/softheprotein.

105. Four levels of structural organization of proteins
Many genetic diseases result from protein with abnormal amino acid sequences. If the
primary structure of the normal and mutated proteins are known , this information may be
used to diagnose or clinical study of the disease.