Biochemistry Lecture Notes PDF

Title: lecture (8) Biochemistry Protein structure and classification Present By: Prof.Ingy Badawy Protein classification according to function Classification of protein according to shape Globular protein: ✓Spherical shape ✓Have an axial ratio less than 10 but not below 3 or 4 ✓Ex: heamoglob...

Title: lecture (8) Biochemistry Protein structure and classification Present By: Prof.Ingy Badawy Protein classification according to function Classification of protein according to shape Globular protein: ✓Spherical shape ✓Have an axial ratio less than 10 but not below 3 or 4 ✓Ex: heamoglobin, enzymes, globin, albumin Fibrous protein: ✓Longitudinal ✓Have an axial ratio greater than 10 ✓Ex: collagen, keratin , elastin Axial ratio= L/W Conjugated proteins  Primary and Secondary Structure Tertiary and Quaternary Structure Protein Hydrolysis and Denaturation 13 Primary Structure of Proteins The particular sequence of amino acids that is the backbone of a peptide chain or protein CH3 CH3 S CH CH3 SH CH2 CH3 O + CH O CH2 O CH2 O - H3N CH C N CH C N CH C N CH C O H H H Ala-Leu-Cys-Met 14 Secondary Structure – Alpha Helix Three-dimensional arrangement of amino acids with the polypeptide chain in a corkscrew shape Held by H bonds between the H of –N-H group and the –O of C=O of the fourth amino acid along the chain Looks like a coiled “telephone cord” 15 Secondary Structure – Beta Pleated Sheet Polypeptide chains are arranged side by side Hydrogen bonds form between chains R groups of extend above and below the sheet Typical of fibrous proteins such as silk 16 Secondary Structure – Triple Helix Three polypeptide chains woven together Glycine, proline, hydroxy proline and hydroxylysine H bonding between –OH groups gives a strong structure Typical of collagen, connective tissue, skin, tendons, and cartilage 17 Learning Check P1 Indicate the type of structure as (1) primary (2) alpha helix (3) beta pleated sheet (4) triple helix A. Polypeptide chain held side by side by H bonds B. Sequence of amino acids in a polypeptide chain C. Corkscrew shape with H bonds between amino acids D. Three peptide chains woven like a rope 18 Solution P1 Indicate the type of structure as (1) primary (2) alpha helix (3) beta pleated sheet (4) triple helix A. 3 Polypeptide chain held side by side by H bonds B. 1 Sequence of amino acids in a polypeptide chain C. 2 Corkscrew shape with H bonds between amino acids D. 4 Three peptide chains woven like a rope 19 Tertiary Structure Specific overall shape of a protein Cross links between R groups of amino acids in chain disulfide –S–S– + ionic –COO– H3N– H bonds C=O HO– hydrophobic –CH3 H3C– 20 Learning Check P2 Select the type of tertiary interaction as (1) disulfide (2) ionic (3) H bonds (4) hydrophobic A. Leucine and valine B. Two cysteines C. Aspartic acid and lysine D. Serine and threonine 21 Solution P2 Select the type of tertiary interaction as (1) disulfide (2) ionic (3) H bonds (4) hydrophobic A. 4 Leucine and valine B. 1 Two cysteines C. 2 Aspartic acid and lysine D. 3 Serine and threonine 22 Globular and Fibrous Proteins Globular proteins Fibrous proteins “spherical” shape long, thin fibers Insulin Hair Hemoglobin Wool Enzymes Skin Antibodies Nails 23 Quaternary Structure Proteins with two or more chains Example is hemoglobin Carries oxygen in blood Four polypeptide chains Each chain has a heme group to bind oxygen 24 Learning Check P3 Identify the level of protein structure 1. Primary 2. Secondary 3. Tertiary 4. Quaternary A. Beta pleated sheet B. Order of amino acids in a protein C. A protein with two or more peptide chains D. The shape of a globular protein E. Disulfide bonds between R groups 25 Solution P3 Identify the level of protein structure 1. Primary 2. Secondary 3. Tertiary 4. Quaternary A. 2 Beta pleated sheet B. 1 Order of amino acids in a protein C. 4 A protein with two or more peptide chains D. 3 The shape of a globular protein E. 3 Disulfide bonds between R groups 26 Protein Hydrolysis Break down of peptide bonds Requires acid or base, water and heat Gives smaller peptides and amino acids Similar to digestion of proteins using enzymes Occurs in cells to provide amino acids to synthesize other proteins and tissues 27 Hydrolysis of a Dipeptide OH + CH3 O CH2 O H2O, H+ H3N CH C N CH C OH H heat OH CH3 O CH2 O + + H3N CH COH + H3N CH C OH 28 Denaturation Disruption of secondary, tertiary and quaternary protein structure by heat/organics Break apart H bonds and disrupt hydrophobic attractions acids/ bases Break H bonds between polar R groups and ionic bonds heavy metal ions React with S-S bonds to form solids agitation Stretches chains until bonds break 29 Applications of Denaturation Hard boiling an egg Wiping the skin with alcohol swab for injection Cooking food to destroy E. coli. Heat used to cauterize blood vessels Autoclave sterilizes instruments Milk is heated to make yogurt 30 Learning Check P4 What are the products of the complete hydrolysis of Ala-Ser-Val? 31 Solution P4 The products of the complete hydrolysis of Ala-Ser-Val are alanine serine valine 32 Learning Check P5 Tannic acid is used to form a scab on a burn. An egg becomes hard boiled when placed in hot water. What is similar about these two events? 33 Solution P5 Acid and heat cause a denaturation of protein. They both break bonds in the secondary and tertiary structure of protein. 34 Protein-misfolding diseases include conditions where a protein: fails to fold correctly (cystic fibrosis, Marfan syndrome, amyotonic lateral sclerosis) is not stable enough to perform its normal function (many forms of cancer) fails to be correctly trafficked (familial hypercholesterolemia, α1-antitrypsin deficiency) forms insoluble aggregates that deposit toxically (neurodegenerative diseases: Alzheimer’s, type II diabetes, Parkinson’s and many more) Protein-misfolding diseases Protein-misfolding diseases Conditions may be : Familial → the disorder is genetically inherited and symptoms appear during childhood ( e.g., Huntington ) Sporadic → patternless and characterized by a late onset. Primarily due to aging or to an incorrect lifestyle. Not associated with gene mutations. (e.g., most of Alzheimer’s and Parkinson’s cases and many more) Transmissible → (e.g., prion disease, spongiform encephalopathies and fatal familial insomnia) Alzheimer’s disease → most common progressive neurodegenerative disorder →massive loss of neurons →Accumulation of Aβ-amyloid protein (extracellular) →Accumulation of tau protein (intracellular) →Formation of amyloid plaques (Aβ ) →Formation of neurofibrillar tangles or NFTs ( tau protein ) Parkinson’s disease Resulting symptoms Muscular rigidity → extreme pain Postural instability Resting tremor Huntington’s disease Polyglutamine disease → mutation encoding for an addition of Q amino-acids Accumulation of the misfolded protein Huntingtin Formation of toxic inclusions in brain cells Degeneration of glutamatergic striatal neurons polyQ inclusion In neocortex Therapeutic solutions 3 main approaches: 1. Inhibition of protein aggregation 2. Interference with post-translational peptide changes before the misfolding/aggregation step 3. Upregulation of molecular chaperones or aggregate-clearance mechanisms