Transcript Protein Structure and Function

Protein Structure and Function
CHAPTER2. From Structure to Function
There are many levels of protein function
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Biochemist: biochemical role of an individual protein
Cell biologist, geneticist: cellular roles judged by the
phenotype of its deletion or signal pathway
Physiologist, developmental biologist: cellular or
organism level
Protein can have many functions on different levels 
ex) tubulin
4 fundamental biochemical functions:
Binding, catalysis, switching and structural elements
2-0. Overview
: The Structural Basis of Protein Function
◈ Protein interaction and function
Figure 2-1.The functions of tubulin
Ex) GTPase(Protein switch) depend on both binding and catalytic function.
2-0. Overview
: The Structural Basis of Protein Function
Radial spoke
Assemblies of microtubules,
dynein and other microtubuleassociated proteins form flagella
that propel sperm
Figure 2-1.The functions of tubulin
Microtubules and associated motor
proteins form a network of “tracks”
on which vesicles are moved around
in cells. Taxol anti-cancer drug
TAXOL

미국 주목나무의 주피(bark)에서 추출한 taxane ring을 가진 alkaloid이다.
Taxol 와 a-, b- tubulin complex 구조

Mechanism of Action
Paclitaxel은 1992년12월에 난치성 난소암의 치료제로 FDA의 승인을 받은 항암제로 세포 내
microtubule의 assembly를 증진시키고 disassembly를 저해함으로써 항암효과를 나타내는 독
특한 약물이다

Paclitaxel은 암세포의 microtubule의 assembly를 증진 시키고 일단 형성된 microtubule을
안정화시켜 polymerization 상태로 남아있게 함. microtubule의 disassembly를 저해하여 유
사분열에 필요한 방추사의 형성을 억제하므로 세포 주기상 암 세포가 G2기와 M기에 머무르게 되
어 cytotoxic effect를 가진다. 이 세포주기는는 방사선에 매우 민감한 주기이므로 radiation
therapy와 병용할 시 cytotoxicity가 증가하게 됨.
2-1. Recognition, Complementarity and Active Sites
◈ Ligand binding
- Ligand or substrate binding is
very specific.
- Specificity arises from the
complementarity of shape
and charge distribution
between the ligand and its
binding site on the protein
surface
Figure 2-2. Substrate binding to anthrax toxin lethal factor
2-1. Recognition, Complementarity and Active Sites
◈ Substrate binding
-Molecular recognition depends on
specialized microenvironments that result
from protein tertiary structure;
Internal cavities, pocket or cleft of surface
-Specialized microenvironments at binding
sites contribute to catalysis;
Lysine in hydrophobic env  as acid
Enzyme favor reaction by providing a
nonpolar environment
-The proximity of these two (Lys164 and Lys166) positive charges lowers the proton
affinity of both of them, making lysine 166 a better proton shuttle for the metal-bound
substrate.
Figure 2-3. Schematic of the active site of mandelate racemase showing substrate bound
2-2. Flexibility and Protein Function
◈ Ligand binding model
-The flexibility of tertiary structure
allows proteins to adapt to their ligands;
Charge configuration, potential H-bond
complementarity
- Lack-and-key analogy : implies
rigidity of the protein(the lock) and of
the ligand(the key)
-Induced fit model : both protein
and the ligands are naturally flexible
Figure 2-4.Tight fit between a protein and its ligand
2-2. Flexibility and Protein Function
◈ Protein structure flexibility
Haloperidol
Crixivan
Peptide analog of
the natural substrate
Each inhibitor clearly has a quite different structure, yet all bind
tightly to the active site(Because of protein structure flexibility)
Figure 2-5. HIV protease, and enzyme from the virus
that causes AIDS, bound to three different inhibitors
2-2. Flexibility and Protein Function
-Protein flexibility is essential for
biochemical function
-Red : increase in enzyme activity
from yeast
-Blue : increase in enzyme activity
from Thermophilic bacteria(optimal
growth rate is at 85℃)
-Balance between flexibility and
rigidity is necessary for protein
activity because stability has been
achieved at the expense of flexibility.
-Genetic engineering in Enzyme?
Figure 2-6. Differences in the temperature dependence of the specific activity of
D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from two organisms
2-2. Flexibility and Protein Function
Some proteins undergo very large shape changes when the correct ligand binds
Figure 2-7. Example of a large conformational change in adenylate kinase
2-3. Location of Binding Sites
◈ Binding sites (concave, convex, or flat)
Growth
hormone
Receptors
Two different protein-protein interfaces can be made by one molecule of
growth hormone with two identical receptor molecules
Figure 2-8.The complex between human growth hormone and two molecules of its receptor
2-3. Location of Binding Sites
Helix-turn-helix motif
Zinc finger
Many binding sites for RNA or DNA on proteins are protruding loops or
alpha helices that fit into the major and the minor grooves of the nucleic
acid
Figure 2-9.Two protein-DNA complexes
2-3. Location of Binding Sites
- Binding sites for small ligands are clefts,
pockets or internal cavities because it
provides microenvironment to block water
access, which is important for many enzyme
reactions and enough contact points to bind
strongly.
- The active site of this enzyme contains a
catalytic heme group(puple) most of which is
completely buried inside the protein.
- protein flexibility open a transient path for
Penetration of the substrate
Figure 2-10. Structure of bacterial cytochrom P450 with its substrate camphor bound
Cytochrome P450
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The cytochrome P450 superfamily (officially abbreviated as CYP) is a large and
diverse group of enzymes. The function of most CYP enzymes is to catalyze the
oxidation of organic substances. The substrates of CYP enzymes include
metabolic intermediates such as lipids and steroidal hormones, as well as
xenobiotic substances such as drugs and other toxic chemicals. CYPs are the
major enzymes involved in drug metabolism and bioactivation, accounting for
about 75% of the total number of different metabolic reactions.[1]
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The most common reaction catalyzed by cytochromes P450 is a monooxygenase
reaction, e.g., insertion of one atom of oxygen into an organic substrate (RH)
while the other oxygen atom is reduced to water:
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RH + O2 + NADPH + H+ → ROH + H2O + NADP+
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Cytochromes P450 (CYPs) belong to the superfamily of proteins containing a
heme cofactor and, therefore, are hemoproteins. CYPs use a variety of small
and large molecules as substrates in enzymatic reactions. Often, they form
part of multi-component electron transfer chains, called P450-containing
systems. Cytochromes P450 have been named on the basis of their cellular
(cyto) location and spectrophotometric characteristics (chrome): when the
reduced heme iron forms an adduct with CO, P450 enzymes absorb light at
wavelengths near 450 nm, identifiable as a characteristic Soret peak.
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CYP enzymes have been identified in all domains of life, i.e., in animals,
plants, fungi, protists, bacteria, archaea, and even viruses.[2][3] More than
11,500 distinct CYP proteins are known.[4]
2-3. Location of Binding Sites
-Catalytic sites often occur at
domain and subunit interfaces
-If a protein has more than one
structural domain, then the
catalytic site can be found at
the interface between them
Figure 2-11. Structure of the dimeric bacterial enzyme 3-isopropylmalate dehydrogenase
2-4. Nature of Binding Sites
◈ Binding site characteristic
-Binding sites generally have a
higher than average amount of
exposed hydrophobic surface
Heme
Large hydrophobic areas on the surface of a protein lead to self-association
And oligomerization. But binding sites for small molecules are usually
too small and concave to allow the protein to oligomerize.
Figure 2-12. Surface view of the heme-binding pocket of cytochrome c6,
with hydrophobic residues indicated in yellow
2-4. Nature of Binding Sites
◈ Week binding and partner swapping
-Weak interactions can lead to an easy
exchange of partners
-Weak interaction → easy to dissociation and
combine with other protein partner → PARTNER
SWAPPING
-STAT molecules are themselves phosphorylated,
and their SH2 domains dissociate from the
receptor and bind to the phosphotyrosine on the
other STAT molecule to form an active signaling
dimer. This results in two SH2-p-Tyr interactions
instead of one SH2-p-Tyr interaction with
receptor. It should Irreversible for signal
transduction
Figure 2-13. Partner swapping in a signaling pathway
2-4. Nature of Binding Sites
◈ Week binding and domain swapping
-Domain swapping is also mediated by
week interaction between domains
-Conformational rearrangement of the
carboxy-terminal arm of the
papillomavirus capsid protein required for
the stable assembly of the virus coat
PAK1 protein kinase is a domain-swapped dimer
-A regulatory domain from each monomer inhibit
the active site of the other monomer.
-When an activator protein (GTP-bound Cdc42) binds to this regulatory domain
-It relieves the domain swapping and frees the active site.
Figure 2-14. Domain swapping in the papilloma virus capsid protein
Displacement of water also drives binding events
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for binding between ligand and protein, water
layer (hydrogen shell) must be disrupted or
partially displaced.
Thermodynamics?
Enthalphy? Between Waters and protein-waters,
in hydrophobic environment
How about entrophy?
2-4. Nature of Binding Sites
◈ Interaction between oleate and lipid-transport protein nsLTP
-Hydrogen bond to the charged head group
-Mainly hydrophobic interaction with the lipid tail
Generally, the affinity between a protein and its ligand is
due to hydrophobic interactions,which are non-directional,
whereas specificity of binding is chiefly due to directional
forces such as hydrogen bonding.
Lipid oleate
Figure 2-15. Ligand binding involving hydrophobic and hydrogen-bond interactions
2-5. Functional Properties of Structural Proteins
◈ Proteins as frameworks, connectors and scaffolds
-In some cases, structural proteins
are assisted by DNA and RNA, lipid
and carbohydrate molecules.
-Ex). Ribosome: has over a hundred
different protein components(for
stabilization, catalytic function)
Blue : protein
Red & grey : RNA
-Dynamics in proteins;
muscle, actin filaments, fibrinogen
Figure 2-16. Structure of the 50S (large) subunit of the bacterial ribosome
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http://www.youtube.com/watch?featur
e=player_detailpage&v=Jml8CFBWcDs
2-5. Functional Properties of Structural Proteins
◈ Some structural proteins only form stable assemblies
Permanent structural proteins
-Silk, collagen, elastin, or keratin
-Collagen : fibrous component of tendons.
Collagen is a triple helix of three protein
chain made up repeating GlyXY sequence(where X is
often proline).
- Hydrophobic interactions, H-bond and cross-linking
of lysine residues (peptidyl aldehydes by lysyl
oxidase)
Figure 2-17. Structure of collagen
2-5. Functional Properties of Structural Proteins
◈ Some structural proteins serve as scaffolds
-In the signal transduction, specific
protein recruitment is required.
-Sometimes this recruitment occurs
by localizing components to the cell
membrane.
-But the other cases specific
structural proteins serve as scaffold
proteins
Figure 2-18.The Ste5p scaffold in MAPK cascade
2-6. Catalysis: Overview
◈ Catalysis and Catalyst
-Catalysts accelerate the rate of a
chemical reaction without changing its
overall equilibrium
-Catalyst : substance that accelerates
the rate of a chemical reaction without
itself becoming permanently altered in
the process
-orotidine 5’-monophosphate
decarboxylase reaction does not occur
readily at room temperature in the
absence of a catalyst.
Figure 2-19. The enzyme orotidine 5’-monophosphate decarboxylase catalyzes the
transformation of orotidine 5’-monophosphate to uridine 5’-monophosphate
2-6. Catalysis: Overview
◈ Catalysis and Catalyst
-OMP decarboxylase is not the
only enzyme that is known to
accelerate a reaction by more than
a billion fold.
Figure 2-20.Table of the uncatalyzed and catalyzed rates for some representative enzymatic reactions
2-6. Catalysis: Overview
◈ Catalysis is reducing the activation-energy barrier to a reaction
- Blue : Uncatalyzed reaction.
single transition-state barrier
- Red : In presence of CATALYST.
additional smaller activation-energy barriers
-The energy required to overcome this
barrier is known as the activation energy
:activation-energy barrier
-The higher activation energy barrier,
the slower the reaction
S
P
Figure 2-21. Energetics of catalysis
-How to overcome the barrier?
2-7. Active-Site Geometry
•Reactive groups in enzyme active sites are optimally positioned to interact
With the substrate
-primarily by van der Waals interactions and complementary H-bonds and electrostatic interactions
-Too tight substrate binding reduces efficiency as a catalyst. Why?
-Specific complex is necessary for productive collision; correct orientation
Which induces atomic orbitals can overlap to allow the appropriate bonds to be formed or broken.
-enzyme offer the time and place for second substrate to bind to enzyme.
Negative substrate
Gated binding
Positive
potential
Figure 2-23. Schematic diagram showing some of the ways in which electrostatic
interactions can influence the binding of a ligand to a protein
2-7. Active-Site Geometry
◈ Active site residues are optimally positioned to interact with the
substrate
This enzyme is shown as a
Active site
homodimer and two active site
-Negative potential on the
protein will repel the negatively
charged superoxide
substrate(O2-)
Active site
Red contour : negative electrostatic potential
Blue contour : positive electrostatic potential
-Positive potential in the active
site will attract it.
Figure 2-22. The electrostatic potential around the enzyme Cu, Zn-superoxide dismutase
2-7. Active-Site Geometry
◈ Specificity sub-site and Reaction sub-site
-Reaction sub-site : enzyme carry out
the chemistry
-Specificity sub-site : enzyme uses
polar and nonpolar groups to make
weak interactions with the substrate.
A.A change in this sites for medical
PLP
and industrial uses
Figure2-24. Schematic diagram of the active site of E.coli aspartate aminotransferase
2-8. Proximity and Ground-State Destabilization
◈ Some active sites chiefly promote Proximity
-Proximity factor : substrate
molecules are intrinsically
reactive. Close to each other
so that the atomic orbitals are
positioned to overlap for the new
Close
together
chemical bond.
Concentration?
Figure2-25. Catalysis of the reaction of carbamoyl phosphate and aspartate by the enzyme aspartate
transcarbamoylase depends on holding the substrates in close proximity and correct orientation in the active site
2-8. Some active sites destabilize Ground-State
Destabilization
-Chorismate mutase for the biosynthesis of aromatic amino acid destabilize
ground states to increase the reaction rate.
-Enzyme promotes the reaction primarily by binding the substrate in an unusual
“CHAIR” conformation
-Compounds designed to mimic this conformation are particularly effective
inhibitors of the enzyme.
Negative charged
carboxylate group in
hydrophobic pocket
Energetically unfavorable
Figure2-26.The pericyclic rearrangement of chorismate to prephenate
via the proposed “chair-like” transition state
2-9. Stabilization of Transition States
and Exclusion of Water
◈ Binding energy
If the transition state can be bound more tightly
than the substrate, activation energy will be reduced
The differential binding of enzyme for these two state
Is the driving force of reactions
a = new interactions with transition state
b = stabilization
ES : enzyme and substrate complex
EP : enzyme and product complex
Substrate and product are of equal energy, with a large free-energy barrier
between them.
Figure2-27. Effect of binding energy on enzyme catalysis
Many active sites must protect their substrates from
water, but must be accessible at the same time
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When an active site is in its closed conformation, it is
protected from water. But substrates, products?
2-9. Stabilization of Transition States
Hydrogen bond
Attack
Acetyl group addition
-Citrate synthase with a different geometry from that of the substrate
-Asp375 and His274 catalyze the formation of the enol of acetyl-CoA
-The acetyl-CoA enol attacks the carbonyl carbon of oxaloacetate
-Addition of the elements of the acetyl group at this portion
Figure2-28.The active site of citrate synthase stabilizes a transition state
with a different geometry from that of the substrate
2-9. Stabilization of Transition States
and Exclusion of Water
◈ Binding and conformational changes
- If an enzyme active site dies not start out perfectly complementary to the
transition state, the enzyme undergo conformational changes that increase
that complementarity
Unliganded PGK
Complex with its substrate
Figure2-29. Phosphoglycerate kinase (PGK) undergoes a conformational
change in its active site after substrate binds
2-9. Stabilization of Transition States
and Exclusion of Water
- Many active sites must protect their substrates from water,
but must be accessible at the same time
-Resting enzyme exist in an open state to which substrates can bind readily
-Substrate binding trigger the conformational changes to the closed form
-Opening and/or closing of the lid is the rate-determining step in the reaction
Hydride ions (H-) are unstable in water, so the active site must be shield
from bulk solvent. Why?
Figure2-30. NAD-dependent lactate dehydrogenase has a mechanism for
excluding water from the active site once substrates are bound
2-10. Redox Reactions
◈ Enzyme chemical reactions
A mammalian cell produces over 10,000 different proteins
→ more than half are enzymes
→ thousands of different enzymes with thousands of different substrates and
products
→ 4 similar reaction
→ Oxidation/reduction
→ addition/elimination
→ hydrolysis
→ decarboxylatoin
2-10. Redox Reactions
1). Oxidation and reduction reaction
→ The oxidation of an alcohol to a ketone by NAD as in the reaction catalyzed
by malate dehydrogenase
→ The oxidation of a satuated carbon-carbon bond to an unsaturated carboncarbon bond by FAD as in the reaction catalyzed by succinate dehydrogenase
Figure2-31. Example of oxidation/reduction reacions
2-10. Redox Reactions
1). Oxidation and reduction reaction
→ In the first step of the pathway for the conversion of cholesterol to pregnenolone
Oxidation by insertion of an oxygen atom
Figure2-31. Example of oxidation/reduction reacions
2-11. Addition/Elimination,
Hydrolysis and Decarboxylation
2). Addition and elimination reaction
→ Addition of water across
the C=C of fumarate to
create the HC-COH group of
malate, a reaction catalyzed
by fumarase. Only L-malate
→ Addition of acetate to the
carbonyl carbon of
oxaloacetate in the aldol
condensation reaction
catalyzed by citrate
synthase
Figure2-32. Examples of addition/elimination reactions
Ordered binding; Oxaloacetate binding induces a major conformational change
Leading to the creation of a binding site for acetyl CoA
2-11. Addition/Elimination,
Hydrolysis and Decarboxylation
3). Hydrolysis reaction
→ Cleavage of the C-N bond of a peptide involves attack by water on the carbonyl
carbon, resulting in formation of a caboxylic acid and an amine (by Protease)
→ Breaking the P-O-R bond of a phosphate diester involves attack by water on the
phosphorus atom, resulting in formation of a phosphate monoester and an alcohol
(by endonuclease)
Figure2-33. Examples of peptide and phosphoester hydrolysis
Serine protease mechanism
Nucleophilic
attack
Tetrahedral
intermediate
(acyl-enzyme)
Amine is free
Substrate binding
Carboxylic acid
product
Water mediated
deacylation
OH- Attacks the
carbonyl carbon
2-11. Addition/Elimination,
Hydrolysis and Decarboxylation
4). Decarboxylation reaction
→ Shortening of the three-carbon unit of pyruvate to the two-carbon unit of
acetaldehyde is accomplished by the loss of CO2, catalyzed by the cofactor TPP
bound at the active site of the enzyme pyruvate decarboxylase
Figure2-34. Example of the decarboxylation of a carboxylic acid
Pyruvate Dehydrogenase Links Glycolysis to the Citric acid cycle
1. Decarboxylation
2. Oxidation
3. Formation of Acetyl CoA
2-12. Active-Site Chemistry
◈ Acid-base catalysis
- Acid : proton
donating group
-Base : proton
accepting group
-Acid-base catalysis :
proton transferring
catalysis
-pKa value : proton
affinity
Figure2-35.Table of pKa values for some common weak acids in biology
2-12. Active-Site Chemistry
pKa=4
pKa=6
-Enzymes can increase the efficiency of acid-base reactions by changing the
intrinsic pKa values of the groups involved
-Two carboxylic acid side chins(Asp and Glu) are found in the active site of
lysozyme
-Glu 35 pKa = 4 in solution, But with no water around to accept a proton, the
carboxylic acid tend to hang on to its hydrogen. pKa=6
Figure2-36. Active site of lysozyme
2-13. Many active sites use cofactors to
assist catalysis
◈ Cofactor and coenzyme
-Not every biological reaction can be carried out efficiently using only the
chemical properties of the 20 naturally occurring amino acids.
Ex) Unpaired electron
-To overcome limitations, many enzyme active sites contain non-aminoacid cofactors that allow specialized chemical functions
-Cofactors can be as small as metal ion / as large as heterocyclic
organometallic complex (Heme)
-Coenzyme : cofactors that are organic compounds and assist catalysis
-Right cofactor binding to the right protein at the right time!!
Figure2-37.Table of organic cofactors
2-13. Cofactors
In humans most cofactors are derived from vitamins and minerals in the diet
Figure2-37.Table of organic cofactors
2-13. Cofactors
Figure2-37.Table of organic cofactors
2-13. Cofactors
Figure2-38.Table of metal-ion cofactors
2-13. Cofactors
Organic cofactor can be synthesized by modification of amino acid side chain
-GFP (green fluorescent protein), chromophore is synthesized by the protein
itself from the reaction of a tyrosine with neighboring serine and glycine.
Lys side chain
-LTQ : unusaul coenzyme in copper
amine oxidase
-LTQ is synthesized by the addition
of a lysine side chain of the
enzyme itself
-Is essential for the proper crossOxidized form of tyrosine
linking of collagen and elastin
Figure2-39.The coenzyme lysine tyrosylquinone
Green fluorescent protein (GFP)
•composed of 238 amino acids (26.9 kDa),
originally isolated from the jellyfish
Aequorea victoria
•fluoresces green when exposed to blue
light
•Used as a reporter of expression &
biosensor
•The GFP gene can be introduced into
organisms (bacteria, yeast and other
fungal cells, plant, fly, and mammalian
cells)
•2008 Nobel Prize in Chemistry : Martin
Chalfie, Osamu Shimomura and Roger Y.
Tsien
•A typical beta barrel structure
Fluorescence of GFP chromophore by
cyclization reaction including
rearrangement and oxidation
2-14. Multi-Step Reactions
◈ Multi-step reaction
To achieve high-energy demanding catalysis, the reactions need to break up
into a number of steps, each of which has a lower-energy transition state
instead of stabilization of transition state.
(a) Use the hydroxyl group of a
serine side chain and nucleophile
attack the carbonyl carbon of the
amide bond
(Ser OH group was activated by His
and close to the substrate.
Asp-His-Ser is called catalytic triad)
Figure2-40.The chemical steps in peptide hydrolysis catalyzed
by the serine protease chymotrypsin
2-14. Multi-Step Reactions
(b) Form the acyl-enzyme intermediate
Oxyanion hole
Figure2-40.The chemical steps in peptide hydrolysis catalyzed
by the serine protease chymotrypsin
2-14. Multi-Step Reactions
(d) Water molecule attacks the
carbonyl carbon of the acyl-enzyme.
Figure2-40.The chemical steps in peptide hydrolysis catalyzed
by the serine protease chymotrypsin
2-14. Multi-Step Reactions
(e) Formation of product.
And Ser on the enzyme is
restored to its original state.
Figure2-40.The chemical steps in peptide hydrolysis catalyzed
by the serine protease chymotrypsin
2-15. Multifunctional Enzymes
◈ Bifunctional (or multifunctional) enzymes
- catalyze more than one chemical transformation
- one or more active sites
- Three classes
1) Two reaction take place consecutively at the
same active site
2) Two separate chemical reactions are catalyzed
by two distinct active sites in different domains
3) Two or more reactions are catalyzed by two or
more distinct active sites which are connected by
internal channels
2-15. Multifunctional Enzymes
Class 1. Bifunctional enzymes have only one active site
Figure2-42.The reaction catalyzed by isocitrate dehydrogenase
2-15. Multifunctional Enzymes
Class 2. Bifunctional enzymes contain two active site
Intertwined homodimer
transformylase
cyclohydrolase
Figure2-43. The bifunctional enzyme, AICAR transformylase-IMP cyclohydrolase (ATIC)
is a single enzyme with two distinct active sites
2-16. Multifunctional Enzymes with Tunnels
Class 3. Some bifunctional enzymes shuttle unstable intermediates
through a tunnel connecting the active site.
; A physical channel allows the product of one reaction to diffuse through
the protein to another active site
Figure2-44.The two active sites of the bifunctional enzyme tryptophan
synthase are linked by an internal channel
2-16. Multifunctional Enzymes with Tunnels
-Carbamoyl phosphate synthetase
-The single-chain protein has three separate
active sites connected by two tunnels
through the interior of the protein
-The entire journey from first substrate to
final product covers a distance of nearly
100Å
Glutamine is hydrolyzed to ammonia
Ammonia + carboxyphosphate (ATP+HCO3-) 
carbamate
Carbamate + ATP  carbamoyl phosphate + ADP
Figure2-45.Three consecutive reactions are catalyzed by the three active sites
of the enzyme carbamoyl phosphate synthetase
Some enzymes have non-enzymatic
functions
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Regulatory functions; transcription factors,
signaling proteins, essential cofactors in protein
synthesis, cytokines or growth factors
Thymidylate synthase also functions as an RNAbinding proteins
- bind to mRNAs including transcripts of the p53
and the myc family genes and repress the
translation of these genes
- Good target for anti-cancer drugs