Navigable Slide Index

1. Introduction
2. Research questions
3. Dihydrofolate reductase
4. Dihydrofolate reductase reaction and structure
5. Kinetic scheme of DHFR catalysis
6. DHFR structures (Swaya and Kraut)
7. Hydride transfer rates data
8. DHFR chain
9. Are the mutations coupled or not coupled?
10. Triple mutant cycle
11. Long range coupling interactions in DHFR
12. Hydride transfer reaction
13. NADPH binding affinity
14. DHFR dynamics by NMR spectroscopy
15. Energy landscape of catalysis
16. Coupled loop motions in DHFR
17. Network of coupled motions in DHFR
18. Link between motions and catalysis
19. Time-resolved conformational changes
20. Conformational changes vs. enzymatic reaction
21. Protein motions occur on many timescales
22. Adenylate kinase' relevant states at equilibrium
23. Fast motion hypothesis
24. Role of electrostatic interactions in catalysis
25. Vibrational spectroscopy for electrostatics
26. Thiocyanate probe
27. Electrostatics in DHFR
28. Electrostatic landscape of enzyme catalysis
29. Electrostatic reorganization in DHFR
30. Frequency and field related by stark tuning rate
31. Decomposition of electric field contributions
32. Conformation – electrostatics – catalysis
33. Major contributors to the electric field
34. Summary
35. Acknowledgments

Topics Covered

• How do enzyme motions and fluctuations impact catalysis?
• Are the times scales for protein structural changes and the enzymatic catalytic cycle similar?
• How are electrostatics modulated in enzyme active sites in conjunction with catalysis?
• Dihydrofolate reductase as a model: kinetics, reactions & structure

Links

Series:

• Chemical Biology
• Protein Epidemiology

Categories:

• Biochemistry
• Cell Biology
• Pharmaceutical Sciences

Talk Citation

Talk Information

• Published on October 1, 2007
• Updated on July 31, 2017