Receptor/enzymes

1. Receptor/enzymes

2. Drug Design • Most drugs work on proteins • Somehow interfere with a biochemical process • Can shut down • Can activate

3. Proteins • Polymers of amino acids that have some function • Enzymes • Receptors

4. Protein structure • Function very dependant on structure • Polymers of amino acids • Huge molecules • Fold back on selves • Held together by weak interactions • Disruption of structure called denaturation

5. Hemoglobin structure example

6. Enzymes • Biological catalysts • Speed up reactions without being consumed

7. Enzymes often involved in metabolic pathways

8. Enzyme mechanism • E + S > ES > EP > E + P

9. Receptors • Molecules on a cell surface • Binding by “ligand” on outside of cell causes changes on the inside of the cell • Molecule brought in • Cellular signalling

10. Receptor binding causes change on inside of cell

11. Drugs • Most drugs work on receptors or enzymes • Problems • Receptor/enzyme works too well • Receptor/enzyme doesn’t work well enough

12. Lock and Key Hypothesis • Protein and ligand have complementary shapes. • Interactions must also be complementary • If enzyme charge is negative, substrate must be positive • If pocket is nonpolar, ligand must be nonpolar

13. I E S I S E Competitive binding • Drug (I) binds instead of substrate/ligand

14. Drug binds instead of substrate • Antagonists • Binding prevents substrate binding • Blocks response • Agonists • Binding of drug instead of substrate elicits response • turns switch on

15. Drugs can bind to other sites • “allo” binding • Can activate • Can deactivate • Can attenuate

16. Inhibition at allo site S I I Inhibitor binds to an allosteric site on the enzyme Changes active site so substrate doesn’t bind

17. Allosteric Activation S S A A • Active site will not bind substrate • Allosteric activator binds and changes shape of active site • Now substrate binds

18. Antibiotics • Bacteria different than human cells • Similar biochemistry

19. Penicillin prevents formation of bacterial cell walls

20. Viruses • Contains DNA surrounded by protective shell or capsid • Uses host cells enzymes and ribosomes for replication • Lysogenic phase: viruses may remain dormant inside host cells for long periods. There is no obvious change in their host cells • Can enter the lytic phase: new viruses are produced, assemble, and burst out of the host cell. • The cell is killed and other cells are infected

21. Typical Viral structure

22. Lytic and lysogenic life cycles

23. Antivirals • Interfere with some aspect of life cycle • Some with attachment • Some with self assembly • etc