Trypsin has a peptide inhibitor called BPTI

8. Trypsin has a peptide inhibitor called BPTI

9. 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?

10. Transition State Stabilization

11. Metal-dependent protease

12. Aspartyl Proteases

13. HIV Protease w/ inhibitor

15. Lysozyme

16. Peptidoglycan layer

18. Oxocarbenium

20. Binding energies of subsites - - - + - -

21. Transition state is half-chair conformation Use lactone as a transition state analog

22. Cleavage sites of HIV protease

23. Model substrate bound to HIV protease

26. Glucose + 2NAD+ + 2ADP + 2Pi 2pyruvate + 2NADH + 2ATP + 2H2O + 4 H+

27. Can be broken into 2 half reactions Glucose + 2NAD+ ∆Gº’1 = -146 kJ/mol 2pyruvate + 2NADH + 2H+

28. Can be broken into 2 half reactions 2ADP + 2Pi ∆Gº’2 = -61 kJ/mol 2ATP

29. ∆Gº’1 = -146 kJ/mol ∆Gº’2 = -61 kJ/mol ∆G’ºs = ∆Gº’1 + ∆Gº’2 = -85 kJ/mol Under actual cellular conditions > 60% of the energy in glucose is recovered as ATP

30. Glucose + 6O2 ∆Gº’ = -2,840 kJ/mol 6CO2 + 6H2O There is much more energy left in pyruvate

35. Induced fit in hexokinase