2. Biochemical Overview on Amino Acids Structure and Protein Structure and Function Dr. Waheed Al-Harizi Medical Biochemistry Department College of Medicine King Saud University

3. What are Proteins? Functions of Proteins Proteins are the most abundant and functionally diverse molecules in living systems. Virtually every life process depends on proteins. Enzymes and hormones Contractile proteins Bone Blood proteins

4. Amino Acids Structure of the amino acids Structure of the amino acids Although more than 300 different amino acids have been described in nature, only twenty are commonly found as constituents of mammalian proteins. Each amino acid has a carboxyl group, an amino group, and a distinctive side chain ("R- group") bonded to the  -carbon atom. Although more than 300 different amino acids have been described in nature, only twenty are commonly found as constituents of mammalian proteins. Each amino acid has a carboxyl group, an amino group, and a distinctive side chain ("R- group") bonded to the  -carbon atom.

7. A. Amino acids with nonpolar side chains

8. B. Amino acids with uncharged polar side chains

9. C. Amino acids with acidic side chains D. Amino acids with basic side chains C. Amino acids with acidic side chains D. Amino acids with basic side chains

13. Structure of Proteins The twenty amino acids commonly found in proteins are joined together by peptide bonds. The linear sequence of the linked amino acids contains the information necessary to generate a protein molecule with a unique three- dimensional shape. The complexity of protein structure is best analyzed by considering the molecule in terms of four organizational levels, namely, primary, secondary, tertiary, and quaternary. The twenty amino acids commonly found in proteins are joined together by peptide bonds. The linear sequence of the linked amino acids contains the information necessary to generate a protein molecule with a unique three- dimensional shape. The complexity of protein structure is best analyzed by considering the molecule in terms of four organizational levels, namely, primary, secondary, tertiary, and quaternary.

15. Primary Structure of Proteins The sequence of amino acids in a protein is called the primary structure of the protein.Understanding the primary structure of proteins is important because many genetic diseases result in proteins with abnormal amino acid sequences, which cause improper folding and loss or impairment of normal function The sequence of amino acids in a protein is called the primary structure of the protein.Understanding the primary structure of proteins is important because many genetic diseases result in proteins with abnormal amino acid sequences, which cause improper folding and loss or impairment of normal function

17. Secondary Structure of Proteins The polypeptide backbone does not assume a random structure, but instead generally forms regular arrangements of amino acids that are located near to each other in the linear sequence. These arrangements are termed the secondary structure of the polypeptide. The  - helix,  -sheet,  -bends, and loops (coils) are examples of secondary structures frequently encountered in proteins. Hydrogen bonds maintain the secondary structure The polypeptide backbone does not assume a random structure, but instead generally forms regular arrangements of amino acids that are located near to each other in the linear sequence. These arrangements are termed the secondary structure of the polypeptide. The  - helix,  -sheet,  -bends, and loops (coils) are examples of secondary structures frequently encountered in proteins. Hydrogen bonds maintain the secondary structure

18. Secondary Structure of Proteins continue……

20. Supersecodary Structures (Motifs)

21. Tertiary Structure of Globular Proteins The primary structure of a polypeptide chain determines its tertiary structure. [Note: "Tertiary" refers both to the formation of domains (the basic units of structure and function, and the final arrangement of domains in the polypeptide.] Domains Domains are the fundamental functional and three- dimensional structural units of a polypeptide. Polypeptide chains that are greater than 200 amino acids in length generally consist of two or more domains.

22. Tertiary Structure of Globular Proteins continue…… Interactions stabilizing tertiary structure 1.Disulfide bonds: These strong, covalent bonds help stabilize the structure of proteins, and prevent them from becoming denatured in the extracellular environment. 2.Hydrophobic interactions 3.Hydrogen bonds 4.Ionic interactions

23. Quaternary Structure of Proteins Many proteins consist of a single polypeptide chain, and are defined as monomeric proteins. However, others may consist of two or more polypeptide chains that may be structurally identical or totally unrelated. The arrangement of these polypeptide subunits is called the quaternary structure of the protein. Many proteins consist of a single polypeptide chain, and are defined as monomeric proteins. However, others may consist of two or more polypeptide chains that may be structurally identical or totally unrelated. The arrangement of these polypeptide subunits is called the quaternary structure of the protein.

24. Denaturation of proteins Protein denaturation results in the unfolding and disorganization of the protein's secondary, tertiary and quaternary structures, which are not accompanied by hydrolysis of peptide bonds. Denaturing agents include heat, organic solvents, mechanical mixing, strong acids or bases, detergents, and ions of heavy metals such as lead and mercury Protein denaturation results in the unfolding and disorganization of the protein's secondary, tertiary and quaternary structures, which are not accompanied by hydrolysis of peptide bonds. Denaturing agents include heat, organic solvents, mechanical mixing, strong acids or bases, detergents, and ions of heavy metals such as lead and mercury

25. Denaturation of proteins ( continue….. Denatured proteins are often insoluble and, therefore, precipitate from solution. Denatured proteins loose their functions. Denatured proteins are often insoluble and, therefore, precipitate from solution. Denatured proteins loose their functions. Certain precautions have to be taken in order to prevent proteins being denatured or inactivated during purification by physical or biological factors Certain precautions have to be taken in order to prevent proteins being denatured or inactivated during purification by physical or biological factors

26. References: Jeremy Berg, John Tymoczko, and Lubert Stryer: Biochemistry, fifth edition WH Freeman and company (New York) Harper’s Biochemistry. Twenty-fifth edition. Eds: RK Murray, DK. Granner, PA. Mayes and VW Rodwell. Lippincott’s Illustrated Reviews, Biochemistry, Fourth edition. Wds: Richard A. Harvey, Pamela C. Champe. Lippincott Williams & Wilkins.