2. overview
Intracellular receptors
Intracellular enzymes and signal
Transduction molecules
Transcription factors
Structural proteins
Nucleic acid
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3. Nucleic acids
These are biopolymers or linear polymers
Nucleic acids is overall name for the DNA & RNA
DNA & RNA mainly composed of nucleotides which
are monomers made of three components
I. 5 carbon sugar unit
II. Phosphate group
III. Nitrogenous compounds
If the sugar part is ribose, the polymer is ribonucleic
acid (RNA)
If the sugar part is deoxy ribose, the polymer is
deoxyribonucleic acid (DNA)
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4. Function of nucleic acid
• To create and encode and then store information
in nucleus of every living cell
• Their function is to transmit and express the
information inside and outside of the cell
nucleus to the interior operations of the cell and
to next generation.
• The encoded information conveyed via the
nucleic acid sequence.
• The nucleic acid sequence provides the ladder
step order of nucleotides within the molecule of
DNA and RNA.
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5. • The nucleotides are bonded to form the
helical structure, one helical RNA and two
helical DNA.
• They are assembled in chains of base pairs of
purines (adenine , guanine) and
pyrimidines(cytosine , thymine and uracil).
• The specific sequencing in DNA of the base
pairs enable storing and transmiting the coded
information as genes.
• In RNA base pair sequencing provided for
manufacturing new proteins.
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6. DNA (DEOXY-RIBO NUCLEIC ACID)
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• DNA is a memory or reserve
bank of genetic information
• It is more stable than RNA ,
hence it is helpful in long
term repository of genetic
information
• It controls every function of
the cell through protein
synthesis
• Replication of DNA is a
process in which the DNA
copies itself to produce the
identical daughter molecules.
7. Structure of DNA
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• It is composed of monomers of dAMP, dGMP, dCMP, dTMP.
• The monomers are held together by 3'-5' phosphodiester
bridges and base pairs are linked to sugar via N- glycosidic
linkage.
• DNA had equal number of (A=T) residues and equal number
of (G ≡ T) is known as Chargaff's rule of DNA composition.
• The two strands are antiparalell, one runs in 5‘ to 3‘
direction while other in 3‘ to 5' direction.
• The width of double helix is 20 A ͦand two strand are held by
hydrogen bonds formed by complementary base pairs.
• For measurement DNA is expressed in terms of base pairs
eg: kb,mb,gb. And the length is expressed in terms of
contour length.
• EXAMPLE: E.COLI - 4.6*109 , Contour length – 1.5 mm
8. RNA(RIBO-NUCLEIC ACID)
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• RNA is a single stranded
polymer of
ribonucleotides held
together by 3'-5'
phosphodiester bridges
• RNA differs from DNA it
has pentose sugar of
ribose and uracil as a
pyrimidine moiety and it
gives colour reaction
with orcinol due to
presence of ribose.
10. Intracellular receptors
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• Receptors that are present inside the cell rather
than surface.
• Many drugs target intracellular enzymes produce
their effect by altering enzyme production of
critical signaling.
• It senses the signals from the lipid soluble
substances and other hormonal substances to
influence the gene expression.
• EXAMPLES:
1. Nuclear receptor.
2. IP3 receptor.
11. NUCLEAR RECEPTOR
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The steps involved in glucocorticoid receptor activation. In the absence of ligand, nuclear receptor (NR) monomers are
bound to heat shock proteins (HSP) to form an NR-HSP complex (1). As the ligand diffuses through the plasma membrane (PM),
HSP is released from the NR-HSP complex. The ligand then binds to its NR enabling it to dimerise with another NR monomer (2).
Depending on the type of cell, the ligand-receptor complex can either produce non-genomic effects by activating for example the PI3
kinase and ERK pathways (3), have a genomic effect (4) or both. The usual cellular functions such as cell growth, proliferation,
differentiation, motility, survival and intracellular trafficking, can be achieved via the PI3 and ERK pathways. Conformational
changes within the NR dimer produces genomic effects by inducing the recruitment of other MTFs [such as activator protein 1
(AP-1); and specificity protein 1 (SP-1)] and co-activator proteins including the steroid receptor coactivator-1 (SRC-1) and cAMP
responsive element binding protein (CBP), to enhance ligand-dependent steroid receptor transcriptional activity (6). These proteins
have an intrinsic histone acetyltransferases (HAT) which facilitates DNA unwinding, enabling RNA pol II access (7) and therefore
promotes gene transcription (8). Co-repressors can modify chromatin structure by recruiting histone deacetylase (HDAC) or a
chromatin remodelling complex to prevent DNA unwinding and hence repress gene expression (5). (Molenda-Figueira et al., 2006)
Key PI3=Phosphatidylinositol 3-kinases; ERK=extracellular-signal-regulated kinases; PM=plasma membrane; NM=Nuclear
membrane.
12. IP3 RECEPTOR
• Ip3 receptor is an ip3 gated ion
channel releases ca²⁺ from the
endoplasmic reticulum
• Ip3 receptor represents a
dominant secondary messenger
leading to release of ca²⁺ from
storage sites
• InsP3R is very diverse among
organisms, and is necessary for
the control of cellular and
physiological processes
including cell division, cell
proliferation, apoptosis,
fertilization, etc
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13. Intracellular enzymes
• Intracellular enzymes are produced and retained
in the cell for the use of cell itself
• They are helpful in various biological activities
and metabolic reactions
• The are found in the cytoplasm, mitochondria
and nucleus
Examples
• RNA polymerase – involved in the transcription
process
• Oxidoreductase – catalyses biological oxidation
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15. Transcription factors
Transcription factors are involved in the initiation of
mRNA production
Basically they interact with the DNA helix to either
facilitate or hinder the access of RNA holoenzyme, DNA
must be unwound so that RNA polymerase II can act to
express the gene.
They have two functional components
1. DBD( DNA binding domain): which binds to highly
conserved sequence in the DNA strand with high affinity.
2. TAD(trans activation domain):where modulator
proteins can interact and influence gene expression.
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16. • The number of transcription factors found within the
organism is depend on their genome size with larger
genomes tend to have more TF’s
• In human approx 10 TF’S can bind to their target
sequence within a single gene
• Whether a gene is expressed or repressed depends
on the individual TF’s and specific members of
transcription factors
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18. classification
1.helix-turn helix:
• This group have three α helix structure with two sub
units antiparallel and at third adjacent to them so that
they can bind to their cognate sequence within the
major and minor grooves
eg: homeo domain protein, pov factors
2.β- scaffold factors:
• They have similar anti parallel structure except they
have two β-sheets that interact with minor groove
contacts eg: rel proteins
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19. 3.Basic domains:
1.Leucine zippers:
• They have two α helix that interact with DNA to form a
scissor like structure
• Interactions of repeat leucine in the carbonyl portions
allows the helixes to form a
2.helix loop helix:
• Similar to leucine zipper except the dimerisation occur via
additonal carboxyl α-helixes that are separated to loops
eg: myogenic transcription factors , cell cycle controlling
factors
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20. 4.Members of zinc fingers:
• This contain loops that are formed due to zn⁺⁺ ions
stabilizing the interaction of cysteine-cysteine or cysteine-
histidine residues
• This loops enables the proteins three α helixes to interact
with their DNA sequences within the grooves
eg: steroid hormone receptors
5.Hmg(high mobility group):
• The main function is the remodelling of chromatin (eg:
bending and wrapping) so that transcription factors can gain
access and is independent of histones
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21. Structural proteins
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• A protein involved in maintaining cytoskeleton
found all over the body
• This function depends on specific association
of the protein subunits with themselves as
well as the proteins, carbohydrates and others
• Structural proteins are also important sources
of biomaterials such as silk , collagen and
keratin
22. Examples of structural protein
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Collagen fibers:
• collagen are the most abundant protein in the human body
• Serves to strengthen the structure as in extracellular matrix or
vitreous humor of the eye
• To provide great strengthen to tendons
keratin:
• fibrous structural protein component of hair , skin and nail
• Cross-linked proteins typically containing α-helix and β sheet motifs
and are high in glycine and alanine content
• Cytoskeleton component of desmosome cellular junction
23. PSG college of pharmacy,cbe.
Myosin:
• ATP-dependent motor proteins
• Major contractile proteins
• Each of heavy chains have a globular head region for a ATP
hydrolysis & actin binding and tail region
• It composed of one or two heavy chains and four or more
light chains
Actin:
• Cytoskeltal and scaffolding for signal transduction process
• Act as track for myosin dependent vesicle and the organelle
transport
• Muscle contraction via ATP dependent myosin walking along
the actin microfilament of the sacromer
