16 th August 2013

1. 16th August 2013

2. carbohydrates, lipids, proteins and nucleic acids “Molecules of life” Packets of instantly available energy Energy stores Structural material Metabolic workers Libraries of hereditary information Cell to cell signals Slides by : J Sen

3. Proteins are communication devices to conduct biological processes

4. Proteins Enzymes – that carry out chemical reactions are largely proteins. Most drugs bind to proteins to repair a ‘faulty bio-machine’ to restore order in the system (organism). How are Proteins made? DNA RNA Protein Cellular processes Transcription Translation

5. Most drugs bind to proteins to repair a ‘faulty bio-machine’ to restore order in the system (organism). HIV drugs that bind to a target protein exploits shape complementarity

6. Isolated Viral Capsid protein Viruses infect by manipulating their proteins Fully formed stable virus particle

8. Proteins play crucial roles in all biological processes Trypsin, Chmytrypsin – enzymes Hemoglobin, Myoglobin – transports oxygen Transferrin – transports iron Ferritin – stores iron Myosin, Actin – muscle contraction Collagen – strength of skin and bone Rhodopsin – light-sensitive protein Acetylcholine receptor – responsible for transmitting nerve impluses Antibodies – recognize foreign substances Repressor and growth factor proetins Slides by : Sankar

9. BiopolymersBuilding Blocks Proteins Amino acids Nucleic acids Nucleotides Carbohydrates Sugars Lipids Fatty acids Proteins Enzymes carry out these reactions.

10. Proteins talk to each other due to shape-complementarity. The shape is important for its function. Proteins are polymers of amino acids

11. Proteins are made up of 20 amino acids NH2 H C COOH R Rvaries in size, shape, charge, hydrogen-bonding capacity and chemical reactivity. – a very small tool kit!! Slides by : Sankar

12. Only L-amino acids are constituents of proteins Slides by : Sankar

13. Nonpolar and hydrophobic Basic Acidic Slides by : Sankar

14. 20 amino acids are linked into proteins by peptide bond Slides by : Sankar

15. Peptide bond has partial double-bonded character and its rotation is restricted. Slides by : Sankar

16. Polypeptide backbone is a repetition of basic unit common to all amino acids Slides by : Sankar

17. YGGFL is a different polypeptide than LFGGY Slide by : J. Sen

18. Large proteins - sequence lengths are long. One letter code is easier to work with than the three-letter codes for amino acids. Slide by : Sankar

19. Proteins Long polymers : from 20 amino acids Primary structure ADDFGFIPRELALKRMKGSTPNY Fold into compact structures

20. Protein Structure: Four Basic Levels • Primary Structure • Secondary Structure • Tertiary Structure • Quaternary Structure Slides by : Sankar

21. Slides by : Sankar

22. An educated guess of the proteins function from the primary sequence Histone (human) SETVPPAPAASAAPEKPLAGKKAKKPAKAAAASKKKPAGPSVSELIVQAASSSKERGGVSLAALKKALAAAGYDVEKNNSRIKLGIKSLVSKGTLVQTKGTGASGSFKLNKKASSVETKPGASKVATKTKATGASKKLKKATGASKKSVKTPKKAKKPAATRKSSKNPKKPKTVKPKKVAKSPAKAKAVKPKAAKARVTKPKTAKPKKAAPKKK Rhodopsin (human) MNGTEGPNFYVPFSNATGVVRSPFEYPQYYLAEPWQFSMLAAYMFLLIVLGFPINFLTLYVTVQHKKLRTPLNYILLNLAVADLFMVLGGFTSTLYTSLHGYFVFGPTGCNLEGFFATLGGEIALWSLVVLAIERYVVVCKPMSNFRFGENHAIMGVAFTWVMALACAAPPLAGWSRYIPEGLQCSCGIDYYTLKPEVNNESFVIYMFVVHFTIPMIIIFFCYGQLVFTVKEAAAQQQESATTQKAEKEVTRMIIMVIAFLICWVPYASVAFYIFTHQGSNFGPIFMTIPAFFAKSAAIYNPVIYIMMNKQFRNCMLTTICCGKNPLGDDEASATVSKTETSQVAPA

23. How does a protein’s three dimensional structure emerge? The primary structure of the protein gives rise to the protein’s shape in the following ways: It allows hydrogen bonds to form between the C=O and N-H groups of different amino acids along the length of the polypeptide chain. It puts “R” groups into positions that allow them to interact. Through their interactions the chain is forced to bend and twist. Slide by : J. Sen

24. The anatomy of the peptide backbone The peptide bond is essentially plannar These atoms are on the same plane. Slide by : J. Sen

25. Second level of protein structure Hydrogen bonds form at short intervals along the new polypeptide chain and they give rise to a coiled or extended pattern known as the secondary structure of the protein. Think of the polypeptide chain as a set of rigid playing cards joined by links that can swivel a bit. Each card is a peptide group. Atoms on either side of it can rotate slightly around their covalent bonds and form bonds with neighboring atoms. Slide by : J. Sen

26. Features: • It is a rod like structure. • Backbone is inside while side chains are on the outside. • Hydrogen bonding between CO and NH groups of the main chain stabilizes the structure. • CO group of residue R hydrogen bonds with the NH group of residue R+4. • Rise per residue is 1.5Å and rotation per residue is 100 degrees, therefore, residues per turn is 3.6. • Most α-helices observed naturally are right-handed helices. Alpha helix (α helix) Slide by : J. Sen

27. Pauling and Corey predicted the structure of α-helix 6 years before it was actually experimentally observed for the structure of Myoglobin. The elucidation of the structure of α-helix is a landmark in Biochemistry because it was demonstrated that the conformation of a polypeptide chain can be predicted if the properties of its constituents are rigorously and precisely known. For this work Pauling got the Nobel prize in Chemistry in 1954. The helical content of a protein may vary anywhere between 0% to 100%. 75% of AAs in Ferritin, an iron storage protein is in alpha-helices. α-helices are usually less than 45Å long. However, two or more α-helices can entwine to form a very stable structure, which can have a length of 1000Å or more. Such α-helical coiled coils are found in many structural proteins e.g. myosin, tropomyosin in muscle, Fibrin in blood, Keratin in hair etc. α-helical coiled coil Slide by : J. Sen

28. Beta sheet (β sheet) Where residues per turn is 2 (n=2) it is a β-pleated sheet structure. There are two kinds of β-pleated sheet structures either the chains (strands) are such that in two successive chains they have same directionality for N>C or they are parallel chains (parallel β-sheet) or they are in opposite/ anti-parallel orientation (anti-parallel β-sheet). • Features: • Distance between two successive amino acids is 3.5Å. • The side chains are at 180° to each other. • Adjacent β-strands are linked by hydrogen bonds. • In antiparallelβ-sheets the hydrogen bonds between the CO and NH of adjacent strands form between groups that are diametrically opposite to each other. • In parallel β-sheets hydrogen bonds between CO group of one amino acids forms with the NH group of two amino acids downstream in the other strand. • β-strands are depicted by arrows schematically. Slide by : J. Sen

29. β-sheet is an important structural element in many proteins e.g. fatty-acid binding proteins, important for lipid metabolism, are almost exclusively built of β-sheets. Many β-strands (4-10 or more) may come together in a protein. These β-strands may be all parallel to each other or anti-parallel or mixed. A and B are ball and stick and ribbon model of the same polypeptide, respectively. β-strands may have twists. Side view of the schematic in B demonstrates the twists. A protein rich in β-sheets, This is a fatty acid binding protein – but not necessary that all fatty acid binding proteins are like this. Slide by : J. Sen