Enzymes as Drug Targets Ch 3 & 7 Flashcards
Enzymes lower the _______ ________ of a reaction by binding tightly to the ________ _____, but not the ___ of the reaction.
activation energy, transition state, delta G
Seven ways in which enzymes function as catalysts
1) Reaction surface; 2) Bring reactants together; 3) Position reactants correctly; 4) Weaken bonds; 5) Acid-base catalysis; 6) Provide nucleophiles for covalent catalysis; 7) Metal ion
PNP specificity
Specific for syn conformation of purine nucleoside.
Amino acid in acid-base catalysis
Histidine (can act as proton sink and source)
Nucleophilic residue (3)
Serine, Cysteine, Threonine
Reversible Competitive Inhibitor Where does it bind? Reaction? Effect of increasing substrate concentration? Similar to substrate? Effects Vmax or Km?
Inhibitor binds reversibly to active site.
No reaction takes place on inhibitor.
Increasing substrate concentration will reverse inhibition.
Similar to substrate.
Increase Km
Irreversible non competitive inhibitor Where does it bind? Reaction? Effect of increasing substrate concentration? Similar to substrate? Effects Vmax or Km?
Binds irreversibly to active site.
Covalent bond formed between inhibitor and enzyme.
Increase substrate concentration has no effect.
Similar to substrate.
Decrease Vmax
Reversible non competitive inhibitors Where does it bind? Reaction? Effect of increasing substrate concentration? Similar to substrate? Effects Vmax or Km?
Binds to allosteric site.
Increasing substrate concentration has no effect.
Induced fit distorts shape of enzyme.
Similar to final product of biosynthetic pathway.
Decreases Vmax.
Cofactors (2 types)
Nonprotein molecule needed for reaction catalyzed by enzyme. May be metal ion or coenzyme.
Coenzyme
Organic molecule cofactor
Prosthetic group
Covalently bound coenzyme
Isozymes + example
Enzymes with different subunits or primary structures that catalyze the same reaction. May have different regulation, activity rate, and structure.
Ex. Prostaglandins produced by cyclooxygenase: COX 1- normal inflammation vs COX 2- rheumatoid arthritis
Feedback control vs Activation control
Final product in pathway allosterically turns of first enzyme.
Post translational modification, such as phosphorylation or ubiquination, needed
Transition State Inhibitors
Where does it bind?
Effect of increasing substrate concentration?
Similar to substrate?
Binds irreversibly to catalytic site.
Increase substrate concentration has no effect.
Not similar to substrate (resembles transition state)
Suicide Inhibitors Where does it bind? Effect of increasing substrate concentration? Reaction? Similar to substrate?
Competitive irreversible inhibitor- binds to catalytic site.
Increase substrate concentration has no effect.
Substrate becomes highly reactive species after enzyme acts on it.
Similar to substrate.
