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Proteins – Structure & Properties MBC 224- Level-3 By Dr.Charles Stephen D Origin of Specificity Function is critically dependent on structure 1ruv.pdb Fold of a Protein Refers to the spatial arrangement of its secondary structural elements (ahelices and b-strands) 1l45.pd b a/b-barrel 4bcl.pd b b-barrel 1mbl.pd b a/b-sandwich Introduction • Proteins are the most abundant and functionally diverse molecules in living systems • All process of life depends on these molecules • Enzymes (proteins) and peptide hormones regulate metabolism in the body • Contractile proteins in muscle permit movements • In the blood, hemoglobin, immunoglobulin and albumin do major function • Proteins are linear polymers of amino acids Proteins: What are they? FUNCTIONS • Structural – Support - connective tissue – Keratin – hair, finger nails • Transport – Hemoglobin Proteins: What are they? • Some Hormones – Coordinate body activity (insulin, growth horm.) • Muscles (actin, myosin) What are they made of? • Proteins are polymers – Poly = many – Polymers = LARGE molecules made of smaller, repeating units, called Monomers • These monomers are made up of C, H, O, N, and some S (carbon, hydrogen, oxygen, nitrogen, sulfur) • Monomers are called Amino Acids… Structure of Amino acids • There are > 300 amino acids exist in nature • But only 20 amino acids are found in all proteins • Each amino acid has a carboxyl group, an amino group and distinctive side chain called R group bonded to the α carbon atom. L-Form Amino Acid Structure Carboxylic group Amino group + H3 N R group COO a - H H = Glycine CH3 = Alanine Juang RH (2004) BCbasics Classification of Amino acids (AA) • Since the amino and carboxyl groups are common for all 20 amino acids, the R group is different for each amino acid. • Hence, based on the R group the AA are classified into four groups, namely (1) Nonpolar side chain, (2) Uncharged polar side chain (3) Acidic side chain and (4) basic side chain amino acids. Non polar side chain AA • There are 9 AA in this group - namely, glycine, alanine, valine, leucine, isoleucine, methionine, proline, phenyalanine & tryptophan. • These groups are hydrophobic (water repellent) and lipophilic. • Therefore, the parts of proteins made up of these amino acids will be hydrophobic in nature. Nonpolar side chain - AA Uncharged, polar AA • Serine, Threonine,, Tyrosine, Aspargine, Cysteine and Glutamine belong to this group. • Serine, threonine and tyrosine have ‘OH’ group in the side chain • Aspargine and glutamine have amide group (CO-NH) and cysteine has a thiol (-SH) group in the side chain which can be hydrophilic in water Uncharged polar side chain AA Acidic & Basic side chain AA • They have a negative charge on the R group • Aspartic acid and glutamic acid are the two AA • The negative group is contributed by carboxyl group – COO• Three AA have a positive charge on their R group, they are histidine, lysine and arginine. Acidic side chain AA Basic side chain AA Classification of Amino Acids by Polarity NONPOLAR POLAR Acidic Neutral Basic Asp Asn Ser Arg Cys Tyr His Gln Thr Lys Glu Gly Ala Ile Phe Trp Val Leu Met Pro Polar or non-polar, it is the bases of the amino acid properties. Juang RH (2003) Biochemistry AA with three letters- single letter Properties of AA • 1. Optical property: The α carbon of each amino acid is attached to four different groups and is, therefore, a chiral or optically active carbon atom. Glycine is exception because its α carbon has two H atoms, so it is optically inactive. • The α carbon can exist in two forms which are mirror image of each other, L form and D form. They are called stereoisomer or enantiomers. • All amino acids found in proteins are L configuration However, D amino acids are found in antibiotics and in bacterial cell walls. Mirror Images of Amino Acid a Mirror image a Same chemical properties Stereo isomers Juang RH (2004) BCbasics Properties of AA contd… • Amino acids in aqueous solution contain weakly acidic carboxyl group and weakly basic amino group. • In addition, the acidic and basic amino acids contain an ionizable group in the side chain • So amino acids are ampholytes, ie, they can act as an acid or a base. • They (in proteins) can act as good buffers in biological systems Properties contd… • Amino acids can form zwitter ions • If the net charge of an amino acid is zero, that form is called a dipolar form or isoelectric form or zwitter ionic form. Environment pH vs Protein Charge Buffer pH 10 9 8 7 Isoelectric point, pI + 6 5 4 3 0 - - Net Charge of a Protein Juang RH (2004) BCbasics Structure of Proteins • The 20 AA found in proteins are joined together by peptide bonds • The linear sequence of the linked AA contains the information to form a protein molecule with a unique three-dimensional structure or shape. • The structure of proteins are described in four levels, namely primary, secondary, tertiary and quaternary. How are proteins constructed • First the Amino acids bond together. • They are joined together by what is known as a peptide bond. Formation of a peptide bond via condensation. H R N H C O C H + N H C O C H OH Amino acid R H Amino acid OH A peptide bond between two amino acids. H N H R C H O C H N H C R O C OH H20 [WATER] A condensation reaction Formation of Peptide Bonds by Dehydration Amino acids are connected head to tail NH2 1 COOH 2 NH2 COOH Dehydration Carbodiimide -H2O O NH2 1 C N 2 COOH H Juang RH (2004) BCbasics Protein construction • When two amino acids join together they form a dipeptide. • When many amino acids are joined together a long-chain polypeptide is formed. • Organisms join amino acids in different linear sequences to form a variety of polypeptides in to complex molecules, the proteins. Amino acid Peptide bond Primary protein structure primary structure This is the linear sequence of amino acids Primary Structure • The linear sequence of amino acids in a protein is called the primary structure. • The sequence is determined by information present in the DNA. Any defect in the genetic code leads to abnormal proteins. Eg: sickle cell anemia. • The amino acids are joined covalently by peptide bonds, which are amide linkage between the α carboxyl group of one amino acid, and α amino group of another by removing one molecule of water. Formation of peptide bond Primary structure contd… • Peptide bonds are not broken by protein denaturation, only with strong acid or base these bonds are broken. The proteases present in the digestive tract cleaves the bond. • The free amino end of a peptide chain is written to the left and called N-terminal end. • The free carboxyl end is written to the right and called C-terminal end. • The AA in a peptide chain is called a ‘residue’ or ‘moiety.’ • The peptide consisting two AA is a dipeptide, three AA, a tripeptide, four AA a tetra peptide and so on. Peptides with few AA are called oligopeptides,10 -50 AA are called polypeptides & >50 AA are called proteins. Secondary protein structure Polypeptides become twisted or coiled. These shapes are known as the secondary Structure. There are two common secondary structures The alpha-helix and the beta-pleated sheet. Secondary protein structure Alpha-helix Amino acid Hydrogen bonds hold shape together Secondary Protein structure [The beta pleated sheet] Amino acid Secondary Structure • When the polypeptide chain assume a regular recurrent rearrangement, then the structure is termed as ‘secondary structure’ • α helix and β pleated sheet are examples of secondary structure • Hydrogen bonds are the main chemical force which maintain secondary structure Tertiary protein structure • This is when a polypeptide is folded into a precise shape. • The polypeptide is held in ‘bends’ and ‘tucks’ in a permanent shape by a range of bonds including: • Disulphide bridges [sulphur-sulphur bonds] • Hydrogen bonds • Ionic bonds. Tertiary protein structure Quaternary protein structure Tertiary & Quaternary Structures • When the polypeptide chain attains a shape with twisting, folding, and super folding in a three dimensional position, then the structure is said to be ‘ tertiary ‘. • Disulfide bond,Hydrogen bond, Hydrophobic interactions are responsible for this structure. • When more than one polypeptide chain, in a protein, attain a three dimensional shape, then it is called ‘quaternary’ structure. Two polypeptide chains are ‘dimeric’, three pp chains are ‘trimeric’ proteins etc. Forces responsible for protein structure • 1.Hydrogen bond: Between the Hydrogen atom and carbonyl oxygen or amide Nitrogen (strong electro negative atoms) • 2.Disulfide bond: is a covalent bond between the sulfhydryl (-SH) group of two cysteine residues. • 3.Hydrophobic interactions: AA with non polar R groups tend to be located in the interior of the structure. • 4.Ionic interaction: Negatively charged group such as COO- can interact with positively charged groups, such as the amino group NH3+ Hydrogen,Ionic & Disulfide bonds Protein Denaturation • Protein denaturation results in the unfolding and disorganization of the protein’s secondary and tertiary structures • The peptide bonds are NOT hydrolyzed, (not broken) • Denaturing agents include, heat, organic solvents, mechanical mixing, strong acids, or bases, detergents, ions of heavy metals such as lead or mercury. • Denatured protein becomes less soluble and gets precipitated. • Denaturation may be reversible. Classification of Proteins There are many ways to classify the proteins. This classification is based on the functions of proteins. 1. Catalytic proteins: enzymes 2. Structural proteins: collagen, elastin, keratin 3. Contractile proteins: myosin, actin, 4. Transport proteins: hemoglobin, myoglobin, albumin, transferin 5. Regulatory proteins: insulin, growth hormone 6. Genetic proteins: histones 7. Protective proteins: immunoglobulin, interferon, clotting factors. Fibrous & Globular proteins • Fibrous proteins are elongated proteins (lengthy) and mostly form the structures like the cell membrane , connective tissue etc • Collagen and elastin are examples, which are present in the skin, connective tissue and blood vessel walls • Globular proteins have specialized functions • Enzymes, Hemoglobin and proteinhormones are some examples.