Made for 4th year class

1. Allosteric Inhibition

2. Conformational change The enzyme switches back and forth between the two forms. They are in equilibrium. Inactive form Active form Allosteric Regulation of Enzymes

3. Conformational change Inactive form Active form Allosteric Regulation of Enzymes Allosteric site Active site

4. When the enzyme is in its inactive form, the allosteric sites on the regulatory subunits can accept inhibitor. Allosteric regulation Inactive form Allosteric Regulation of Enzymes Catalytic subunit Regulatory subunit

5. Allosteric regulation Inactive form Allosteric Regulation of Enzymes Catalytic subunit Regulatory subunit Allosteric inhibitor

6. When the enzyme is in its active form, the active sites on the catalytic subunits can accept substrate. Allosteric regulation Active form Allosteric Regulation of Enzymes

7. Once a site is filled with a substrate or inhibitor, binding at a second site of the same type is favored. Cooperativity Allosteric Regulation of Enzymes Substrate

8. Cooperativity Allosteric Regulation of Enzymes No product formation Product formation

13. Structure of ACTase

16. Tertiary and quarternary conformational changes in ACTase No substrate Low affinity T state Substrate binding induces T -> R transition

17. DRUG DESIGN

20. TRADITIONAL DRUG DESIGN Lead generation: Natural ligand / Screening Biological Testing Synthesis of New Compounds Drug Design Cycle If promising Pre-Clinical Studies

22. Structure-based Drug Design (SBDD) Molecular Biology & Protein Chemistry 3D Structure Determination of Target and Target-Ligand Complex Modelling Structure Analysis and Compound Design Biological Testing Synthesis of New Compounds If promising Pre-Clinical Studies Drug Design Cycle Natural ligand / Screening