Enzyme Mechanisms Flashcards
1
Q
Acid-base catalysis
A
Use of amino acid side chains to protonate and deprotonate the substrate
2
Q
Covalent Catalysis
A
- Metal ions make water a better nucleophile
- Makes water a better acid, so it deprotonates more easily
3
Q
RNase A
A
- General acid-base catalysis
- Catalyzes the hydrolysis of RNA
- Reaction goes through the 2’-3’ cyclic nucleotide
- Two His residues catalyze reaction
- Ping pong sequence
4
Q
Carbonic Anyhdrase
A
- H2O + CO2 = HCO3- + H+
- Uses a Zn2+ ion bound by His residues
- Zn2+ deprotonates water to make a hydroxide ion and stabilizes the negatively charged transition states or intermediates
5
Q
Covalent Catalysis
A
- Reaction pathway altered to include covalent enzyme-substrate complexes
- Strong nucleophile and good leaving group
- Nuc could be amines, imidazole, or thiols
6
Q
Lysozyme
A
- Preferential binding of the transition state
- Covalent catalysis
- Catalyzes the hydrolysis of bacterial cell walls
7
Q
Aspartic Proteases
A
- Pepsin, chymosin, cathepsin D, renin, HIV-1 protease
- All involve two Asp residues at the active site
- Two Asps work together as general acid-base catalysts
- Most have a tertiary structure
- HIV-1 protease is a homodimer
8
Q
Aspartic Protease Mechanism
A
- pKa values of Asp residues are crucial
- One has low pKa, other has high pKa
- Deprotonated Asp acts as general base
- Protonated Asp acts as acid
9
Q
HIV-1 Protease
A
- Cleaves the polyprotein products of the HIV genome
- Active site is two-fold symmetric
10
Q
Drug Design
A
- Any drug might be an inhibitor that mimics the transition state for the reaction catalyzed
- These inhibitors also cause the loops over the active site to stick to the enzyme blocking the inhibitor from leaving the active site
11
Q
Hammerhead Ribozyme
A
- Minimal active hammerhead secondary structure
- Metal ions are not required for catalysis, but they do bind
- Any positive ion including ammonium helps stabilize the structure
