1
,
CR
11-15-99
Outline for today's lecture
III.
Catalysis
Enzymatic catalysis
5. Case Studies
- Hexokinase and "Induced Fit"
- Alcohol Dehydrogenases and Stereospecificity
- Lysozyme
- Serine Proteases
Reading Assignments: pages 300-316, 284-286
in Voet, Voet & Pratt
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Summary
- Some enzymes undergo a conformational change upon binding of
the substrate. This is referred to as induced fit.
- Induced fit can be advantageous in cases where this energy-costly
"move" prevents side reactions such as the hydrolysis of ATP.
Hexokinase is an example of an enzyme where this is the case.
- Enzymes are stereospecific, even toward prochiral substrates. This
has been shown for alcohol dehydrogenases, enzymes that catalyze
the oxidation of alcohols, including ethanol.
- Lysozyme and serine proteases are well studied enzymes. The
former catalyzes acetal cleavage with a combination of general acidbase catalytic groups. The latter catalyze amid bond cleavage in a
ping pong mechanism involving an acyl-enzyme intermediate.
- Transition state analogs may be derived from reaction
intermediates whose structure is similar to the transition state. Since
the acetal cleavage reaction catalyzed by lysozyme goes through a
transition state similar in structure to the oxo-carbenium ion
intermediate, a lactone with an sp2 hybridized C-1 can be a good
inhibitor.