Protein Biochemistry : A

Brief Introduction

Dr. Mohamad Sadikin DSc

Department of Biochemistry and
Molecular Biology
FKUI
 The origin of the protein name is a Greek word
προτεοσ (proteos), means the first, the most
important or the most eminent
 → based on the fact : the substances is the most
abundant compound found in any dried living matter or
cell (the 2nd after water)
 → logically, the most abundant compound should
have the most important function
 The importance of prot. roles in realising 3 most basic
life signs, compared to other macromolecules can be
seen in the next table
 Movement Multiplicati Gradient
on
Lipids (-) (-) (+)

Nucleic (-) (+) (-)

acid
Polysachar (-) (+) (-)
ide
Protein (+) (+) (+)
 Other life signs or functions can be added
as much as we will,
 But practically for whatsoever life function
there will be practically at least one
protein corresponding to each function
 Life functions may be very different each
other: structural function is passive,
whereas metabolism or movement is very
active one
 Very important question : how a type of
molecule can support and carry out very
different, even contradictory functions
(active vs passive) ?
 The phenomenon can not be explained solely by
the size of protein molecule (a macromolecule)
 → DNA (a nucleic acid) is the largest macromolecule in
the cell, but DNA carries out only 1 function
 The explication should be looked for in the shape of the
protein
 If this is the case, the question must be reformulated
and sharpened :
 → how a protein, as a macromolecule, but not the other
macromolecule, could take a great variety of shape as
reflected by its functions ?
 The answer must be searched in the nature
of protein molecule itself
 → Definition : protein is heteropolymer of
amino acids, bound each other by
peptidic bond, occupe their strict position
and all are the results of the expression of
information contained in gene (information
unit in the genome or all the DNA strand)
Key words : heteropolymer, amino acid, peptidic bond,
gene expression
 Amino acid
 Amino acid is an organic compound
posessing an acid as well as a basic group
(NH2) in its molecule
 But not every any amino acid can form a
protein, a protein forming amino acid must
fulfill the following criteria :
1.The acid moeity must be a carboxylic group
 → Consequently, any aa whose acid group is
not carboxylic one,i.e sulfate (as in taurin)
will never be found in whatever protein
2.The carboxylic and the amino groups must be bound to
a same C atom : Cα → a protein forming aa has to be an α-aa
 → an aa other than α-aa is excluded
 A general structure of an α-aa :
H
2HN-Cα-COOH

R
 As Cα is an asymmetric C atom (because it binds 4 different

atom or groups), any α-aa can be exist in 2 stereoisomer or

configuration : either L or D
3.Only L-aa can form a protein
 But there a number of L α-aa, metabolically
very important, who are never found any protein
(i.e citruline and ornithin)
4.A L-aa can form and be found in any protein, if and
only if the aa has a specific genetic sign in gene,
named as codon (gene itself can be considered as
an information unit in a DNA molecule or genom
 Any codon code only 1 aa, however the reverse
statement is not true : any protein forming aa may
have > 1 codon
 Until now it is known that there are only
20 aa found to build any protein from
various source of life being (from bacteria
or even from virus to human)
 This is a very extraordinary phenomenon :
one of some universalities in life being (2
others are universality of genetic letter or
codon and in ATP as energy currency)
 → what is valid for virus or bacteria, is valid also
for human.
Amino Acid Classification
 Despite its relatively few types, it is
more aa must be classified for the
convenience of our understanding
 There 2 ways to classiffy protein
forming aa :
1.According to capability of our body
to synthetize any given aa
2.According to physicochemical
nature of R groups
 The capability of the body to synthesize aa :
 → 2 groups of aa :

1.Essentials aa
2.Nonessentials aa
 Essentials aa : an aa is considered essential if it can not be
synthetized by the body
- → it must be supplied by the food
 Nonessentials aa : all the aa that can be synthesized by the body

- → it does not net be in the food

Note: nonessentials aa does not mean not important. Both groups

are important
 Peptidic bond
 There several possibilities to bind an aa to
another aa :
- By an acid anhydridic bond
- By a hydrazidic bond
- By a peptidic bond

 Peptidic bond is much more stable than 2

other bond
 Peptidic bond can also be prolonged practically
infinitely
 In reality, to form a protein, aa are bound
each other only by peptidic bond
 It can be said that peptidic bond is the
backbone of every protein, whereas the
aminoacids are its building blocks
 Chemically, a peptidic bond is :
 Analogue to an esther bond (instead of –OH, it
is –NH2 which form covalent bond with –COOH)
 Formed as a condensation of a –NH2 group of a
molecule of an aa with a –COOH group of
another molecule of an aa by removing a water
(H2O) from both groups
 Formation of a peptidic bond :
H H
 R1-C-COOH + R2-C-COOH →
NH2 NH2

H OHH
 R1-C-C-N-C-COOH + H2O
NH2 R2
 Organization of a protein
molecule
 A protein is not only composed of a
well arranged of aa in a certain
sequence
 It is also build by interaction of various
gtoups found in constituent aa such as
CO (found as part of peptidic bond),
-NH (also part of peptidic bond), and
various form of R group (acidic, basic,
hydophylic and hydrophobic)
 The interactions obey physical rule :
1.Same charge repel each other
2.Opposite charge attract each other
3.Hydrophobic moieties aggregate each other and avoid
water and hydrophilic molecules or moieties.
 Results :

- Various geometric pattern in segment or part of

polypeptide / protein molecule (secondary structure)
as well as in the whole molecule itself (tertiary
structure)
- The primary structure is the arrangement of aa in a
protein
 Note:
 The sole determinant of primary str (aa sequence) is
the gene.
- → once it is formed, it can not be changed any more
- Only change in gene can change 1 aa on a protein → mutation
 On the other hand, the higher structures are very susceptible to
the environtment variations, especially pH & to :
- Any change in 1 or more environtment factors modify the higher
structure
- The higher str is easier to be changed by environtment than the
lower str
 Biological function of any protein is determined by
the 3 D strt (tertiary str)
 Change in 3 D str must disturb the biological
function of the protein →
 denaturation : loss of 3D str (=tertiary str or
conformation) is the result of any env modif (pH,to,
organic solvent, heavy metals such Pb, Cd, Hg etc, uv or
x-ray or even any simple physical treatment as fort
shaking) and always conduct to decrease or even loss of
specific biological activity or function of the protein. More
severe denaturation result in decrease of the protein
solubility.
*Geometric forms of secondary structures :
 As a result of the interactions between various R group
of adjacent aa, some geometric str will be formed
locally (in a segment) or in the whole molecule
 It is well known that there are 5 geometric form in the
secnd strc :
- α-helix
- β-sheet
- Loop
- Bent
- Random coil
* Geometric forms of the global structure (3 D or
tertiary structure) of protein :
 There are only 2

 Each 3 D strc indicates the general function of any

protein. The 3 D str:
- Globular→ globular protein : proteins whose ratio horizontal
axe : vertical axe are between 1 - 2
- Fibrous protein : the ratio are >10
- Generally, globular proteins are regulator protein
(enzyme,mediator,transporter etc)
- Fibrous proteins are structural or supporter protein
(collagen,keratin etc)
 Relations among the various str :
- If a protein has > 1 secondary structure, then it
is a globular protein. Consequently, it is regulator
protein
- On the contrary, if it is consisted only of 1
secondary protein, then it is a fibrous protein.
Consequently, it is a structural or support protein
- Change in 1 aa (primary str) will change the local
interaction berween adjacent R group → change in
second str → tertiary str → perturbation or even loss of
biologisal (i.e. in sickle cell anemia)