1. Chap 10. Conformational Change, Allosteric Regulation, Motors, and Work
Conformation changed
for controlling the activity of regulatory proteins
for interconverting mechanical work and physicochemical free energy
The coupling of conformation change and chemical reaction
pumping ligands against chemical gradients
synthesizing ATP from chemical potentials

2. A. Positive Cooperativity
Sigmoid curve
The characteristic of the cooperative binding of ligands
ex. oxygen binding to myoglobin
Allosteric enzymes
Example: hemoglobin
Four polypeptide chain, a2/b2
Four successive binding constants
Greater fourth oxygen binding constant ( fold)

3. allosteric effectors: inhibitor or activator that that is generally different from the substrate and binds to its own site away from the active site
homotropic effectors: interactions between identical substrate molecules that affect affinities
heterotropic effectors: interactions between allosteric effectors and substrate that affect substrate affinities

4. B. Mechanisms of Allosteric Interactions and Cooperativity
Deoxyhemoglobin and oxyhemoglobin
Changes in quaternary structure:
a units rotate relative to each other through 15 º
Small tertiary structural changes

5. The Models of Cooperative Interaction
The Monod-Wyman-Changeux (MWC) concerted mechanism
The Koshland-Nemethy-Filmer (KNF) sequenctial model
Eigen model
Nested cooperativity

6. The Monod-Wyman-Changeux (MWC) Concerted Mechanism
The simplest model
Concerted, all or none, two-state
Assumption
The protein is an oligomer
The protein exists in either of two conformational states, T and R, in equilibrium
The T state has a lower affinity for ligands
All binding sites in each state are equivalent and have identical binding constants

7. Koshland-Nemethy-Filmer sequential model (KNF)
More accurate for some systems
Assumption
One conformation in the absence of ligands
Conformational change upon binding. The change transmitted to neighboring vacant subunits
Sites NOT SYMMETRIC

8. Eigen model: the General Model
fully asymmetric
the most complex
difficult to work with