Biochemical Overview Biochemical Overview ononAmino Acids Amino Acids Structure and Structure and Protein Structure and Protein Structure and FunctionFunction

Dr. Waheed Al-HariziDr. Waheed Al-HariziMedical Biochemistry Department Medical Biochemistry Department College of Medicine College of Medicine King Saud UniversityKing Saud University

What are Proteins?What are Proteins?Functions of ProteinsFunctions of ProteinsProteins are the most abundant and functionally Proteins are the most abundant and functionally diverse molecules in living systems. Virtually diverse molecules in living systems. Virtually every life process depends on proteins. every life process depends on proteins.

Enzymes and hormonesEnzymes and hormones Contractile proteinsContractile proteins BoneBone

Blood proteinsBlood proteins

Amino AcidsAmino Acids

Structure of the amino acidsStructure of the amino acids

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

A. Amino acids with nonpolar side chainsA. Amino acids with nonpolar side chains

B. Amino acids with uncharged B. Amino acids with uncharged polar side chainspolar side chains

C. Amino acids with acidic side C. Amino acids with acidic side chainschains

D. Amino acids with basic side chainsD. Amino acids with basic side chains

Structure of ProteinsStructure of Proteins

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

Primary Structure of ProteinsPrimary Structure of Proteins

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

Secondary Structure of Secondary Structure of ProteinsProteins

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

Secondary Structure of Proteins Secondary Structure of Proteins continue……continue……

Secondary Structure of ProteinsSecondary Structure of Proteins continue……continue……

Supersecodary Structures (Motifs)Supersecodary Structures (Motifs)

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.]

DomainsDomains 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.

Tertiary Structure of Globular Proteins Tertiary Structure of Globular Proteins continue……continue……

Interactions stabilizing tertiary structureInteractions stabilizing tertiary structure

1.Disulfide bonds: These strong, covalent 1.Disulfide bonds: These strong, covalent bonds help stabilize the structure of bonds help stabilize the structure of proteins, and prevent them from becoming proteins, and prevent them from becoming denatured in the extracellular environment.denatured in the extracellular environment.

2.Hydrophobic interactions2.Hydrophobic interactions

3.Hydrogen bonds3.Hydrogen bonds

4.Ionic interactions 4.Ionic interactions

Quaternary Structure of Quaternary Structure of ProteinsProteins

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

Denaturation of proteinsDenaturation of proteins

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

Denaturation of proteins ( continue…..Denaturation of proteins ( continue…..

Denatured proteins are often insoluble Denatured proteins are often insoluble and, therefore, precipitate from solution. and, therefore, precipitate from solution. Denatured proteins loose their functions.Denatured proteins loose their functions.

Certain precautions have to be taken in Certain precautions have to be taken in order to prevent proteins being denatured order to prevent proteins being denatured or inactivated during purification by or inactivated during purification by physical or biological factorsphysical or biological factors

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.