| Proteins Proteins ate made of amina acids. Amino acids are made of the five elements CH O NS. The general stru lure of an amino acid molecule is shown below. There is @ central carbon atom (called the “alpha carbon"), with four different chemi cal groups attached to t + ahydrogen atom, The R represenis a ferent attaches + abasic amino group ‘molecule for each ‘ype of amino acid. |} + an acidic carboxyl group + variable 'R* group (or side chain) Amino acids are so-called because they have both amino groups and acid groups, which have opposite ch arges. At neutral pH (found in most lving organisms), the groups are ionised as shown above, so there is @ positive charge at one end of the molecule and a negative charge at the other end. The overall net charge on the molecule is therefore ze 0. A molecule like this, with both positive and negative charges is called a -zwitterion The charge on the amino acid changes with pl low pH (acid) neutral pH high pH (alkali H H H NHP—C-COOH = NH3—C—COO ~~ NH.—€ —Ccoo R R R charge — +1 charge — 0 charge = -1 Itis these changes in charge with pH that explain the effect of pH on enzymes. A sold, crystallised amino acid has the uncharged structure ‘Structure of proteins ‘The basic structure of a proteinis e polypeptide chain. Many amino acids (from as few as forty, toa few h Undred) join together by means of peptide bonds in a specific sequence (order) to form a polypeptide chal n. There are 20 different amino acids found in proteins, yet over tens of thousands of different possible proteins. This variety is possible because there are over 8 000 ways that 20 amino acids can be arranged in a tripeptide, ie just 3 amino acids. with longer proteins, the number of possibilities is staggering!| L Peptide bond Formation Two armino acids join in 8 condensation reaction to form a dipeptide. The peptide bond forms between the carboxyl group of one amino acid and the amino group of the next amino acid Below, the process of pep ‘tide bond formation has been ilustrated in an animation. -xes| eae iss amino acid | Amino acid Dipped Wa Did you notice that once again the reverse reaction, hydrolysis, would break the peptide bond upon the ad dition of water- giving two amino acids from one dipeptide? When two amino acids join together a dipeptide is formed, Three amino acids form a tripeptide. Many ami ro acids form a polypeptide. Ina polypeptide there is always one end with a free amino (NH) group, called the N-terminus, and one end ‘with @ free carboxyl (C02) group, called the C-terminus. A polypeptide chain represents the basic structure of aprotein, known as the primary structure. Protein Structure Polypeptides are justa stiing of amino acids, but they fold up to form the complex and well-defined three- dimension al structure of working proteins. To help to understand protein structure, itis broken down into f our levels: 1. Primary Structure “The primary structure of @ protein is the number and sequence of amino acids held together by peptide bo nds in 2 polypeptide chain, “The sequence of amino acids of a protein determines its specific shape and therefore its biological funct lon. This sequence is dictated by the sequence of bases on DNA. 2 Secondary Structure “This is the coiling or folding of the polypeptide chain upon itse | 5 Se | ifs aresultof hydogen bonding between amino acids nthe C—O ——5—=— HN chain, I H bond I The two most common sec ondary structure motifs are the a-hellx and the 8 pleated-sheet ~] T| L The a-helix. The polypeptide chain is wound round to forma helix. Itis held together by hydrogen bonds running parallel ‘with the long helical axis between every fourth pep ‘tide bond ie, amino acid 1 bonded to amino acid 5. There are so many hydrogen bonds that this is @ ve Dates ry stable and strong structure. Do not confuse the crhelix of proteins with the famous double helbx of DNA Helices are cornmon stu ctures throughout bi ology. ‘The B pleated-sheet. The polypeptide chain zig: zags back and forward f corming a sheet of antiparallel strands. Once again ‘tis held together by hydrogen bonds. It makes upt he dense core of many globular proteins e.g. sos Tertiary Structure, + Whenthe helix or pleated sheet structure bends and folds back on itself into a more compact, precise s hape, the protein has a tertiary structure held together by different kinds of bonds. It forms a compact gl obular structure «© Every protein has a unique tertiary structure, which is responsible forts properties and function. Forexa imple the shape of the active site in an enzyme is due to its tertiary structure. © The tertiary structure is held together by bonds between the R groups of the amino acids in the protein, a rnd so depends on what the sequence of amino acids is. © There are three kinds of bonds involved: * hydrogen bonds, which are weak. + ionic bonds between R-groups with positive or negative charges, which are quite strong, + sulphur trong. idges (disulphide bond) - covalent $-$ bonds between two cysteine amino acids, which ares there might also be Hydrophobic interactions between R groups of amino acids Qstn: Explain the significance of the R groups of different amino acid to protein structure [3] Ans: Myoglobin has a tertiary structure and is referredto as a globular protein, since it is folded into a spherical shape. Myoglobin is shown an the right. So the secondary st ructure is due to backbone inte actions andis thus largely independent of primary sequence, while tertiary structure is due to side chain interactions and thus depends on the amino acid sequence. ~] Tuaternary Structure This structure is found in proteins containing more than one polypeptid hain, and simply means how the different polypeptide chains are arrang ogether. This specific shape is again held together by hydrophobic interactions, rogen and ionic bonds. Haemoglobin sa protein with a quaternary structure. Both haemoglobi rnd myoglobin would also be classified as conjugated proteins because y both have @ non-protein group in their structure. Haem - an iron-contal vrs rorpren en 9 9 group is the pros thetic (non-protein) part for both myoglobin and haemoglobin. edt hyd ma thelI 18. Understand the role of ionic, hydrogen and disulphide bonds in the structure of proteins as illustrated by insulin and collagen ‘The specific three dimensional shape (secondary, tertiary, quaternary structure) of a protein is maintain by three types of chemical bonds between R groups of amino acids 1. Hydrogen bonds: Occur between some H atoms (having a slight positive charge) an oxygen and nitrogen atoms (having a slight negative charge). Although these bonds are weak, the lange number of bonds maintains the three dimensional shape. nic bonds: Occur between — COOH groups and — NH) groups found in the R groups. They are stronger than H bonds , but can be broken by changes in pH and temperature 3. Disulphide bond: Some amino ac tne and jionine contain sulphur atoms in the R- groups. Disulphide bonds nin Ke ‘atoms of amino acids that are close together. These bonds are: strong of structural proteins like collagen, They are also useful in linking the t seine pug ins of insulin together. Dinulphide ridge lene bend (weaker isk) (Covalent Boo = strong ik) Hydrogen bend ‘very weak ink) Peptide bene fami acid Nk Note: Hydrophilic and hydrophobic interactions also help to maintain the shape of globular proteins in water (solution). The Mravenene(@) hydrophobic (water hating) parts of the polypeptide chain face away from water by folding inwards. The hydrophilic parts of the chain remain on the surface of the globular structure. ver ero) FIBROUS AND GLOBULAR PROTEINS |_l FIBROUS GLOBULAR Repetitive regular sequence of amino acids Tegular Sequence of amino acids ‘Actual sequence vary slightly between two exarmpl | Sequence highly and never varies between two exe es of same protein mples of the same protein Polypeptide chain form long parallel strands at cert | Polypeptide chain folded into a spherical shape ain intervals Length of chain may vary into two examples of the | Length always identical in two examples of the sa same protein ime protein Stable structure Relatively unstable ‘Support and structural functions ‘Metabolic functions insoluble Soluble(form colloidal suspensions) Secondary structure most wital ite /no tertiary sir Tertiary structure most important ueture High tensile strength Lower tensile strength Haemoglobin ‘© Found in red blood cells where itis used for oxygen trans portation around the body It is a compact globular protein which is made up of 4 polypeptide chains interlocking to make the quatemary structure + The 4 polypeptide chains(2 a and 2 B cheins)are identical conjugated proteins each consisting of 2 globular protein (globulin) attached to a haem unit © Each achain has 141 amino acids and each B chain has 146 amino acids, © Each of these polypeptide chain has a similartertiary structure to that of myoglobin © Haemoglobin has four haem groups and on each @ molecule of oxygen can be cartied therefore hy aemoglobin can carry 4.02 molecules (8 oxygen atoms) ‘©The haem groups comprise of prophyril ring containing an atomof Fe © The Fe(i) atom combines reversibly with an oxygen molecule to form oxyhaemoglobin ©The quertenary structure is the most important jen © Afibrous protein consisting of 3 helical polypeptides that are super-coiled to form a rope lke stru cture of great tensile strength Le. the triple helix ©The secondary structure is the most important in determining the overall structure © Each chain is in the form of a loase helix (not a helix) Denaturation of proteins © Denaturation is the loss of the shape of a protein -it unfolds. As @ result, it canno longer perform its normal biological function. ©The aminoacid sequence does not change ie. the primary structure is not affected ‘© Involves breaking of the weak hydrogen and ionic bonds