F 2006 BIOC 3405

1. F 2006 BIOC 3405 09-28-06

2. Dynamic Protein Function • Structure of protein changes during function • Interactions of proteins with other molecules

3. Terms • Enzyme – a protein which catalyzes a reaction • Substrate – molecule (usually small) upon which enzyme acts • Ligand – molecule (usually small) which interacts with a protein • Binding site – locus of interaction of protein and ligand

4. Example • Proteins and oxygen • Myoglobin (storage) • Hemoglobin (transport)

5. Means • System used: • Heme • Porphyrin ring system • Fe2+

9. Protein-Ligand Equilibrium • (To be compared with Enzyme-Substrate interaction) •  is the fraction of binding sites occupied by ligand • Kd is the dissociation constant (The smaller it is, the stronger the binding)

14. Heme, O2 held in place by (fairly) weak interactions in Mb • His E7 (H bond) – coordinates O2 • His F8 coordinates Fe2+ • Phe CD1, val E11 hydrophobic bonding to porphyrin ring

17. 4 5 6 2 3 8 1 7 9

18. 11 fairly strong 12 much weaker

19. Salt bonds

21. T = tense, R = relaxed

27. Koshland et al MWC

28. Hb as X-porter (X not O2) • H+ HHb+ + O2 HbO2 + H+ • CO2 CO2 + H2N-CHR-CO~  H+ + -O2C-HN-CHR-CO~

31. O2 binding reg’d by 2,3-bisphosphoglycerate • Reduced affinity of Hb for O2 • At high altitudes, 2,3BPG increases