Amino acid, peptide and proteins

Sunday, January 8,

2017Rajesh Chaudhary | Lecturer

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Department of Biochemistry, Nepalgunj Medical College, Nepal

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Amino acids

Asparagine: Asparagus

Glutamate: Wheat gluten

Tyrosine: Cheese

Glycine: Sweet in tasteSunday, January 8,

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Essential AA vs Non-essential AA

Phenylalanine

Valine

Tryptophan

Threonine

Isoleucine

Methionine

Histidine

Arginine

Leucine

Lysine

Rest of the amino acids of 20 common are non-

essential !

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Structural feature of AA

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Non-polar side chains

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1.Do not bind

2. Do not give off

protons

3. Do not participate in

hydrogen bond or ionic

bonds

4. Thought as oily or

lipid-like property that

promotes hydrophobic

interactions

Location of non-polar AAs in proteins

Rajesh Chaudhary | Lecturer

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AA with uncharged polar sidechain

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Albumin and Disulfide bond

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Structure of albumin

is stabilized by the

disulfide (-S-S) bond.

Amino acid with acidic side chain

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Amino acids with BASIC side chain

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Classification of AA

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Abbreviations and symbols

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Optical properties of AA

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Amino acids act as “acids” and “bases”

As ACID

As BASE

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Acidic and basic properties of AA

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Titration of AA

ALANINE


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Amino acids differ in their acid base property

Most of the AA with chiral center and non-ionizable R-

group behaves just like Glycine.

Difference in pKa values reflects on the effect of R-group.

AA with ionizable R-group have complex titration curve

compared to non-ionizable R-group AA.

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Titration of Glycine

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Absorption of UV by AA

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Uncommon amino acids

4-hydroxy proline

5-hydroxy lysine

Methyllysine: myosin, contractile protein

g-carboxylglutamate: prothrombin

Connective tissues

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Structure

Peptide and Protein

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Formation of peptide bond by condensation

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How long a peptide and protein can be, and what can be its molecular weight?

Biologically active peptide have vast

range of size and composition.

Oxytocin (9 AA): p. pitutiary

Thyrotropin-releasing hormone (TRH)

(3 residue): hypothalamus

Amanitin: poisonous mushroom

Can we calculate number of residues in a protein?

Ans.: YES! molecular weight/average molecular weight of a single

peptide. Sunday, January 8,


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Some protein contains groups other

than AADefinition of conjugated protein

Prosthetic group

Conjugated proteins are classified according to chemical

nature of prosthetic group

Glycoprotein

Lipoprotein

Metalloprotein

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Structures of Proteins

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Primary structure of PROTEIN

All covalent bond (mainly polypeptide and disulfide)

20 – 30% of protein in human is POLYMORPHIC.

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Primary structure of proteins

1. Peptide bond

1.1. Naming peptide

1.2. Charactersticks of peptide bond

1.3. Polarity of peptide bond

2. Determination of AA composition of polypeptide.

3. Sequencing of the peptide from its N-terminal end.

4. Cleavage of polypeptide into smaller fragments.

5. Determination of protein’s primary structure by DNA

sequencing.

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Peptide bond and its characteristics

1. Breaking a

peptide bond.

2. Naming peptide

3. Nature of

peptide bond

4. Polarity of

peptide bond

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NOTE: When polypeptides are named all AA have their residues suffixes (-ine, -

an, -ic, or –ate) changed to “-yl” with exception of C-terminal residue.

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Polarity is net zero charge with uneven distribution of that charges !

Secondary structure of PROTEIN

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Helical turns

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a-helical structure

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1.Hydrogen bond.

2.Amino acid per turn

3.Amino acids that that disrupts a-

helix

Stability of a-helix

Alanine shows greater propensity to

make a-helix.

AA in side chain affect: long chain of

Glutamate prevent a-helix formation.

+ve charge on Lys & Arg, repeals each other

prevents a-helix formation.

Glycine occurs frequently in a-helixes.

Reason: flexibility

Stability of a-helix

is affected by the

following factors:

1. Bulkiness of R-

group

2. Charge on side

chain

3. Presence of Proline

AA.

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Amino acids that disrupts a-helical

structure

Proline: inserts kink in the structure which is incompatible

with the smooth helical structure.

Large number of charged amino acids: Glutamate,

histidine, lysine, aspartate

Bulky side chain: tryptophan, valine, isoleucine.

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Why does a-helix form more readily

than any other possible conformation?

Because it makes use of internal hydrogen bond (except

those @ the end of helix)

Structure is stabilized by hydrogen bond formed by

hydrogen atom attached to electronegative nitrogen atom

of a peptide linkage and electronegative carbonyl oxygen

atom of the fourth AA on the amino-terminal side of that

peptide bond.

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Comparison between a-helix and b-pleated

a-helix b-pleated sheet

1. Hydrogen bonds are parallel

to imaginary axis.

1. Hydrogen bond are

perpendicular to axis.

2. Peptide chain: contains

single peptide chain.

2. Contains 2 or more

polypeptide chain.

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b-turn

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Tertiary structure of protein

Types of tertiary protein

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Fibrous Globular

Forces stabilizing tertiary structure of

protein

1. Disulfide bond

2. Hydrophobic interaction

3. Hydrogen bond

4. Ionic interactionSunday, January 8,


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Disulfide bond and Hydrophobic interaction

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Hydrogen bonds and hydrophobic interaction

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Common structural motif

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Steps in protein folding

Formation of secondary structure Formation of domains

Formation of final monomer

protein

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Protein misfolding

Amyloidoses

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Protein misfolding

Alzheimer’s disease

Refolding and misfolding of b-amyloid protein leading to self-aggregation of protein accumulation of protein in brain

Prion disease

Transmissible spongiform encephalopathies (TSEs)

Bovine Spongiform Encephalopathy (BSE)

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Protein degradation – proteasomal

degradation

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Proteins are stabilized by several forces

1. Hydrophobic effect has greatest influence in protein

stability.

2. Electrostatic interaction contribute to protein stability.

3. Disulfide bonds cross-link extracellular proteins.

4. Ionic interaction.

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References

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Amino acid, peptide and proteins

Science

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