Protein Structures Pharmaceutical Biochemistry PDF

General Structure Characteristics of Proteins General definition - Naturally-occurring, unbranched polymer in which the monomer units are amino acids Specific definition - Peptide in which at least 40 amino acid residues are present The terms polypeptide and protein are used interchangeabl...

General Structure Characteristics of Proteins General definition - Naturally-occurring, unbranched polymer in which the monomer units are amino acids Specific definition - Peptide in which at least 40 amino acid residues are present The terms polypeptide and protein are used interchangeably to describe a protein Several proteins have >10,000 amino acid residues Common proteins contain 400–500 amino acid residues Small proteins contain 40–100 amino acid residues General Structure Characteristics of Proteins Based on Polypeptide Chain Present Monomeric: Protein which contains one polypeptide chain Multimeric: Protein which contains two or more polypeptide chains oOne kind of chain: Homomultimer o>1 kind of chain: heteromultimer o hemoglobin is a heterotetramer composed of 2 α-chains and 2 β- chains ▪ Hetero – α and β chains ▪ Tetra – 2 α-chains + 2 β-chains  General Structure Characteristics of Proteins Based on Chemical Composition Simple protein: Protein in which only amino acid residues are present Collagen Albumin  Based on Chemical Composition Conjugated protein: Protein that has one or more non-amino-acid entities (prosthetic groups) present in its structure One or more polypeptide chains may be present Non-amino-acid components may be organic or inorganic Based on Chemical Composition May be classified further based on the nature of prosthetic group(s) present Lipoprotein contains lipid prosthetic groups Glycoprotein contains carbohydrate groups Metalloprotein contains a specific metal as its prosthetic group  Based on Shape Fibrous proteins – α-keratin & collagen The polypeptide chains are arranged in long strands or sheets Long rod-shaped or string-like molecules that can intertwine with one another and form strong fibers that are water insoluble. Structural functions  Based on Shape Globular proteins – myoglobin & hemoglobin The polypeptide chains are folded into spherical or globular shapes Nonpolar AAs are in the interior, polar AAs are on the exterior. Water soluble character allows movement through the blood and other body fluids to sites where their activity is needed. Dynamic functions  Based on Function Catalytic proteins Transmembrane proteins Defense proteins Storage proteins Transport proteins Regulatory proteins Messenger proteins Nutrient proteins Contractile proteins Structural proteins  Based on Amino Acid Contents COMPLETE PROTEINS contains the essential AA in the proper amounts INCOMPLETE PROTEINS is low in one or more of the essential amino acids, usually lysine, tryptophan or methionine. Proteins from animal sources are complete, except gelatin Proteins from vegetable sources are incomplete, except soy protein  Based on Amino Acid Contents COMPLEMENTARY PROTEINS are incomplete proteins which when served together complement each other and provide all the essential amino acids Protein Structures Protein Structures  Protein Structures Four Types of Structures Primary Secondary Tertiary Quaternary Primary Structure of Proteins Primary structure: Order in which amino acids are linked together in a protein Every protein has its own unique amino acid sequence Frederick Sanger sequenced and determined the primary structure for the first protein (insulin) in 1953  Primary Structure of Proteins Primary Structure of a Human Myoglobin  Primary Structure of Proteins Order in which amino acids are linked together in a protein through peptide bonds. It is distinctive of a protein (or polypeptide) and tells its AA composition. It defines the structure, shape and function of the protein. Starts with N-terminal (left) side to C-terminal (right) The sequence is dictated by the DNA base sequence gene. Errors in the DNA may result to erroneous, non-functional protein.  Primary Structure of Proteins Primary structure of a specific protein is the same within the organism Structures of certain proteins are similar among different species of animals Example: Insulin from pigs, cows, sheep, and humans are similar but not identical  Primary Structure of Proteins Immunological reactions gradually increase over time because animal insulin is foreign to the human body Human insulin produced from genetically engineered bacteria is available  Primary Structure of Proteins Peptide linkages are essentially planar, 6 atoms lie in the same plane (C=O, C-N and N-H) Planar peptide linkage structure is rigid, thus rotation of C-N group is hindered; cis-trans isomerism is possible (the trans being highly favored) The effect is peptide bond planarity resulting to zigzag arrangement with a protein backbone The coplanar relationship of the atoms in the amide group is highlighted by the imaginary shaded green plane lying between adjacent α-carbons.  After the primary level, the polypeptide starts to fold. All the information necessary for folding the peptide chain into its “native conformation” is contained in the primary amino acid structure of the peptide. The polypeptide or the protein needs to achieve its “native conformation” to function. The secondary structure, thus, results.  Secondary Structure of Proteins The ordered 3D arrangements or regular folding in localized regions of a polypeptide chain Spatial arrangement of the atoms in the polypeptide chain Formed and stabilized by H-bond between the amide proton and carbonyl O.  Secondary Structure of Proteins The primary structure dictates the secondary structure. The only bond responsible for the secondary structure of proteins is H-bonding between peptide bonds, the –C=O of the one peptide group and the –N-H of another peptide linkage farther along the backbone.  Secondary Structure of Proteins Types: Alpha-helix (α helix) and beta-pleated sheet (β pleated sheet) Alpha helix Single protein chain resembling coiled spring (helix) by H bonds H-bonding between AA within the same chain (intramolecular H-bonding) R group stay outside the helix because there is not enough space for them to stay inside. The helix is tightly wound that the space in the center is too small for solvent molecules to enter. Must have the same conformations (all D or all L) or will not coil  Beta-pleated sheets “Pleated” or zigzag pattern Completely extended protein chain segments in same or different molecules governed by intermolecular (between molecules) or intramolecular (within the molecule) H-bonding R or side chains are below or above the sheet and backbone is alternating top and bottom position. U-turn structure is the most frequently encountered. Beta-pleated sheets Intermolecular H-bonding can be Parallel –chains run in the same direction Antiparallel –chains runin opposite direction which makesit more stable because of fully collinear H-bonds. Secondary Structure of Proteins Unstructured segments Portions of protein with neither alpha helix or beta pleated sheet structure Confers flexibility to proteins, i.e. they interact with several different substances. Tertiary Structure of Proteins The overall 3D shape of a protein Results in interactions between AA side chains that are widely separated from each other. This defines the biological function of the proteins.  Tertiary Structure of Proteins Proteins may have, either the two forms: Fibrous (insoluble) – mechanical strength, structural components, movement Globular (soluble) – transport, regulatory, enzymes In general 4 types of interactions are observed Disulfide bonding Electrostatic interactions H-bonding Hydrophobic interactions  Types of Stabilizing Interactions Disulfide bonds Covalent, strong between cysteine groups, the strongest tertiary bonds. Link chains together and cause chains to twist and bend.  Types of Stabilizing Interactions Electrostatic interactions Aka Salt bridges Acidic R groups and Basic R groups give rise to this H-bonding Between polar, acidic and/or basic R groups H attaches to highly electronegative atom, i.e. O, N, or F Hydrophobic attractions Between non-polar side chains 3D structure of a 3rd protein  Tertiary Structure of Proteins INTERACTIONS NATURE OF BONDING Hydrophobic Interactions Interactions between non-polar groups Hydrophilic Interactions Attractions between polar or ionized groups and water on the surface of tertiary structure Electrostatic Interactions/Salt Ionic interactions between ionized acidic and basic Bridges amino acids Hydrogen Bonds Occur between H and O or N Covalent Disulfide Bonds Strong covalent links between sulfur atoms of two cysteine amino acids Tertiary Structure of Proteins Quaternary Structure of Proteins Refers to organization among the various polypeptide chains in a multimeric protein Highest level protein organization Present only in proteins that have 2 or more polypeptide chains (subunits). Subunits are generally independent of each other (not covalently bonded). Aka oligomeric proteins  Quaternary Structure of Proteins Contain even number of subunits. Produced by electrostatic interactions, H-bond and Hydrophobic interactions Protein Structures STRUCTURAL LEVEL CHARACTERISTICS Primary Sequence of amino acids Secondary The α-helix, β-pleated sheet, or a triple helix forms by hydrogen bonding between peptide bonds along the chain Tertiary A protein folds into a compact, three-dimensional shape stabilized by interactions between R groups of amino acids Quaternary Two or more protein subunits combine to form a biologically active protein