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 (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 2
nd

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 Multiplicat
ion
Gradient
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 (NH
2
) 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 : C

a protein forming aa has to

be an -aa
an aa other than -aa is excluded
A general structure of an -aa :
H

2
HN-C

-COOH
R
As C

is an asymmetric C atom (because
it binds 4 different atom or groups), any
-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 -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 NH
2
which form
covalent bond with COOH)
Formed as a condensation of a NH
2

group of a molecule of an aa with a
COOH group of another molecule
of an aa by removing a water (H
2
O)
from both groups


Formation of a peptidic bond :
H H
R
1
-C-COOH + R
2
-C-COOH
NH
2
NH
2


H O H H

R
1
-C-C-N-C-COOH + H
2
O
NH
2
R
2

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 & t
o :
- 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,t
o
, 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 :
- -helix
- -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)


Terima kasih
Syukran katsira
Thank you veri much
Merci beaucoup
Vielen dank
Gracias
Thararank you