Trypsin has a peptide inhibitor called BPTI

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Trypsin has a peptide inhibitor called BPTI
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Trypsin is still active without Ser195!!!!
If you mutate any of the three residues in the
catalytic triad you still have an enzyme that is
10,000 fold faster than uncatalyzed rxn.
How?
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Transition State Stabilization
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Metal-dependent protease
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Aspartyl Proteases
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HIV Protease w/ inhibitor
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Lysozyme
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Peptidoglycan layer
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Oxocarbenium
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Binding energies of subsites
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Transition state is half-chair conformation
Use lactone as a transition state analog
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Cleavage sites of HIV protease
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Model substrate bound to HIV protease
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Glucose 2NAD 2ADP 2Pi
2pyruvate 2NADH 2ATP 2H2O 4 H
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Can be broken into 2 half reactions
Glucose 2NAD
?Gº1 -146 kJ/mol
2pyruvate 2NADH 2H
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Can be broken into 2 half reactions
2ADP 2Pi
?Gº2 -61 kJ/mol
2ATP
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?Gº1 -146 kJ/mol
?Gº2 -61 kJ/mol
?Gºs ?Gº1 ?Gº2 -85 kJ/mol
Under actual cellular conditions gt 60 of the
energy in glucose is recovered as ATP
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Glucose 6O2
?Gº -2,840 kJ/mol
6CO2 6H2O
There is much more energy left in pyruvate
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Induced fit in hexokinase
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