Lecture- Protein Modified

8/8/2019 Lecture- Protein Modified

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AMINO ACIDS AND

PRIMARY STRUCTUREOF PROTEINS

Dexter F. Pajarito, MPH, PhD (in progress)

Instructor, Chemistry Department

Adventist University of the Philippines


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Functions of Proteins

Functions as enzyme- biological catalyst

Storage and Transport

Support and Shape Mechanical work: movement of flagella

and separation of chromosomes.

Play in decoding information in the cell.

Hormones

Antibodies.


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pKa= -log Ka

pH= pKa

IONIZATION OF AMINO ACIDS


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-When pH of the solution is below the

pKa, the protonated formpredominates.

H3+NCH-COO-

-When the pH s the solution is above

thepKa, the unprotonated form

predominates

H2NCH-COO-


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Nomenclature

ine orate = replaced with yl e from asparagine, glutamine, and

cysteine will be replaced with yl.


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-helix

Cumulative effect of H-bond within the a-

helix maintain the conformation

H-bonding is stable in hydrophobic interiorof protein. (water do not enter, cant

compete with hydrogen bonding)

Side chains are pointing outward

Affected by the identity of the side chains.


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Example:

Ala, fits well into helical conformation

Gly, destabilizes a-helix structure

Pro, least common residue in a-helix dueto its rigid cyclic side chain.

Lacks H-atom in its amide nitrogen

Cant fully participate in helical H-bonding Found at the end of the protein.


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TERTIARY STRUCTURE OF

PROTEINS

It is the overall three-dimensionalshape that results from the

attractive forces between amino

acid side chains (R groups) thatare widely separated from each

other within the chain.


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1. COVALENT DISULFIDE BONDS- strongest tertiary

structure interactions, results from the SH of two

cysteine molecules reacting with each other to form

covalent disulfide.

2. ELECTROSTATIC ATTRACTION- also called SALTBRIDGE. It involves amino acids with charged side

chains.

3. HYDROGEN BONDS- Results when two polar side

chains are close to each other (OH, NH2, COOH,CONH2)

4. HYDROPHOBIC INTERACTIONS-Results when two

non-polar side chains are close to each other.

ATTRACTIVE FORCES:


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QUATERNARY STRUCTURE OF

PROTEINS

-Highest level of protein organization

-It is found in proteins with two or more

polypeptide chains

-It involves the associations among the

separate chains in the oligomeric

proteins.


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Protein Denaturation and

Renaturation

Denaturation-disruption in the native

conformation of protein with loss of biological

activity.

Heat-will result to unfolding and loss of sec.

structure

Normal proteins-stable at 50-60 degree C

Chemicals: chaotropic and detergents Chaotropic- allow H2O to solvate nonpolar

group in the interior of proteins.


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Detergents (hydrophobic tails) penetratethe protein interior and disrupting

hydrophobic interactions


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HYDROLYSIS OF

PROTEINS

-Peptide bonds are hydrolyzed

-Addition of strong acid or base

-Heated above normal temperature

-Due to the action of intestinal

enzymes


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HEMOGLOBIN and MYOGLOBIN

Myoglobin-small monomeric protein that

facilitates the diffusion of oxygen in

vertebrates

-Responsible for oxygen in muscle tissues.

Myoglobin-member of globins-interior: hydrophobic val, leu, ile, phe and

met


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-Both are O2 binding-proteins

-contain 4 subunits (2 alpha and 2 beta

chains)

-Alpha chains- contain 141 AA each

-Beta chains- contain 146 AA each

-Heme-serves are prosthetic group.


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Heme:

-Consist of tetrapyrole ring called

protoporphyrin IX complexed with iron.

-Bound iron (Fe2+)


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Hemoglobin

More complex than Mb

It poses quarternary structure Alpha and beta globin

X diff ti l d


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X-ray diffraction revealed :

1.Alpha and beta chains

have identical tertiary

structures

2.Different vertebrates

have the same tertiarystructures

3.Alpha and beta chains of

hemoglobin are similar to

myoglobin. They have

the same capacity to bind

oxygen in their biological

functions


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O2 is poorly soluble in water. For example, only around 3.2 mL O2is soluble in 1 L blood plasma. By contrast, the proteinhemoglobin (Hb), contained in the erythrocytes, can bind a

maximum of 220 mL O2 per liter70 times the physically soluble

amount.

FACTS:

Four of the six coordination sites ofthe iron in hemoglobin are occupied

by the nitrogen atoms of the pyrrol

rings, and another is occupied by a

histidine residue of the globin (the

proximal histidine). The irons sixthsite is coordinatedwith oxygen in

oxyhemoglobin and with H2O in

deoxyhemoglobin.


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O2 TRANSPORT BY HEMOGLOBIN

-O2 is picked up from the lungs and forms oxyhemoglobin.

-It leaves the lungs saturated with O2 (@high partial O2pressure)

-@ low partial O2 pressure, O2 separates from Hb, formingreduced Hb or HHb.

So,

-If PO2

is high = Hb has higher affinity with O2

(98%

saturated)

-At lower PO2 = Hb has lower affinit for O2 (partially

saturated)


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.four subunits of Hb act cooperatively in binding

oxygen.

T taut/tense state, it resists the binding with O2 (lower

affinity)

R- relaxed state, binding is facilitated. (higher affinity)

First O2 requires to break electrostatic attractions between

subunits.

Conformational change happens that allows other subunits

to bind O2 more rapidly- known as POSITIVE

COOPERATIVITY


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The sigmoidal shape of

hemoglobin's oxygen-

dissociation curve

results from cooperative

binding of oxygen to

hemoglobin.


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ALLOSTERIC MODULATORS

1.Increase in 2,3-DPG/BPG (RBC)

-allosteric effector. Lowers the affinity ofdeoxyhemoglobin for O2

2.Proton Binding- known as Bohr effect

-lowers pH inside red blood cells.

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Lecture- Protein Modified