بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم

2. Proteins

3. Definition of proteins • Levels of organization of protein structure • Structure-function relationship • Protein folding, stability and denaturation • Protein misfolding and diseases

4. Proteinsare the most • Abundant & • functionally diverse • molecules in living systems. • Proteins are organicnitrogenous substances composed of: • carbon, • hydrogen, • oxygenand • nitrogen.. O C N H

5. Functions of proteins: A. Dynamic functions B. Structural(static) functions

6. A. Dynamic functions include : • Transport  glucose - calcium - oxygen. • Catalyticrole: enzymes chemical reactions • Metabolicregulations: by hormones e.g.Insulin, T3 & T4. • Contraction of muscles: by myosin & actin. • Protection: Immunoglobulins - Mucin- Blood clotting factors • Storage: ferritin iron.

7. B. Structural functions: = (static function) • Proteins are structural components of cell membrane, cytoplasm, cell organelles and nuclei. • Mechanical support: • collagenand elastin: in ligaments, tendons and blood vessels. • Keratin in skin, hair and nail. • Osseinenters in the structure of bone.

8. The conformation of proteins(orders of protein structure) • In its native form, protein molecule has a characteristic three dimensional shape (primary, secondary, tertiary structure),  required مطلوبfor biological function or activity. • Proteins formed of 2 or more polypeptide chains have quaternary structure.

11. Primary structure of proteins • This refers to the number & sequence of amino acids(A.A.) in the polypeptide chain (or chains) linked by peptide bonds. • A. A. sequences are read fromN-terminal (amino acid number 1) to C-terminal ends of the peptide. 1 • Abnormal A. A.sequences many genetic diseases e.g.Sickle cell anaemia.

13. Secondary structure of proteins: • Coiling, folding or bending of the polypeptide chain leading to specific structure kept by interactions of amino acids close to each other in the sequence of polypeptide chain. • There are twomain regular forms of secondary structure; • alpha-helix • beta-sheets or bends, .

14. Secondary structure of proteins: • Coiling of the polypeptide chain alpha-helix (e.g. collagen & Keratin) • foldingor bending of the polypeptide chain  beta-sheets or bends, . 2 1

15. Tertiary structure of proteins: • It is the three dimensional structure of each polypeptide chain. (3D) • There are two main forms of tertiary structure:fibrousand globular types.

16. Quaternary structure of proteins • Certain polypeptides will aggregate to form one functional protein. • Proteins possess quaternary structure if they consist of 2 or more polypeptide chains, structurally identical , or totally unrelated united by non-covalent bonds

17. Protein folding • A Specialized group of proteins, named chaperonesare required for the proper folding of proteins. • Depends on interactions between the side chains of amino acids • It occurs within the cell in seconds to minutes. • As a peptide folds, its amino acid side chains are attracted and repulsed according to their chemical properties. • In addition, interactions involving hydrogen bonds, hydrophobic interactions, and disulfide bonds all exert an influence on the folding process.

18. - + + + • - • - interactions which influence folding disulfide bonds. hydrogenbonds, Ionic bonds hydrophobicinteractions,

20. Denaturation of proteins • It means loss of the native structure of proteins ( loss of the protein's secondary, tertiary and quaternary structures,) which are not accompanied by hydrolysis of peptide bonds.  with unfolding and disorganization • Denaturing agents include • heat, • organic solvents, • mechanical mixing, • strong acids or bases, • Denaturation may be either • Reversible (rare)  [Renaturation will occur] • Irreversible (common type) so,  proteins, are permanently disordered. • Denatured proteins are often insoluble precipitate from solution.

21. Protein Misfolding • Protein folding is a complex, trial-and-error process that can sometimes result in improperly folded molecules. • Misfolding of proteins may occur spontaneously, or be caused by a mutation in a particular gene, which then produces an altered protein

22. Protein Misfolding • Dysfunction of • quality control system (Chaperons) Accumulation of intracellular or extracellular aggregates of misfoldedproteins. • Deposits of these misfolded proteins are associated with a  number of diseases including the amyloidoses.

23. In addition some apparently normal proteins can, after abnormal proteolytic cleavage, take on a unique conformational state that leads to the formation of long, fibrillar protein assemblies. • Accumulation of these spontaneously aggregating proteins, called amyloids, has been implicated in many degenerative diseases—particularly in the neurodegenerativedisorder, (= Alzheimer disease)

25. Proline • imino acid • Has a secondary amino group Amino acids have primary amino group except?????

26. Classification of amino acids According to: • Reaction : Neutral , acidic and basic • Bilologically : Essential or non essential • MetaboplicFate: Glucogenic , ketogenic, or both • sidechain properties

28. L-amino acids – natural amino acids found in protein • D-aminoacids are found in antibiotics (like Gramicidin-S, Actinomycin-D and Valinomycin) and in plant and bacterial cell walls • Glycine an exception- no optical activity

29. Sickle Cell Disease • It is a pathology that results from : the substitutionof polarglutamate bythe non-polarvaline inthe B subunit of hemoglobin

30. Collagen – a triple helix A fibrousprotein Part of connective tissues: bone, teeth, cartilage, tendon, skin, blood vessels Contains three left-handed coiled chains Three residues per turn: -Gly-X-Y (X= proline, Y=hydroxyproline or hydroxylysine)

31. Collagen – a triple helix Abnormal Collagen in Scurvy: due to vitamin C deficiency Glycine and Proline in collagen Rich in glycine & prolinea.a. Proline facilitates helical conformation of each α-chain by causing kinks Glycine , the smallest a.a. fits into the restricted spaces where the three chains of the helix come together

32. thank you