First midterm: next Wednesday (10/18) 7 pm in MacKenzie 240C
Midterm will cover thru today (lectures 1-9, homework 1-3, lab 1-3).
Homework sections 3.4 and 3.5 will not be on the exam
How do almost identical receptors distinguish between almost identical steroids?
Binding specificity is discrimination between steroids.
Specificity is determined by:
Affinity measures how strong the interaction is between molecules
Specificity measures the difference in affinity between two (or more) molecules
Estrogen receptor has high affinity for estrogen, low affinity for testosterone
ER is specific for estrogen relative to testosterone
Chen et al. (2004) JBC 279(32):33855-33864Steroids have only a small range of blood concentrations
ER estrogen affinty is tuned to is physiological concentrations
ER testosterone affinity is not
The concentration of estrogen at which the receptor is half saturated is the $K_{D}$
Why is it useful for the $K_{D}$ for estrogen to be near its physiological concentration?
Receptor can change signal a change in concentration to the cell
Biochemists use dissociation constants ($K_{D}$) to measure binding affinity
$ML \rightleftarrows M + L$
$M$ is macromolecule (protein)
$L$ is ligand (small molecule)
$K_{D} = \frac{[M][L]}{[ML]}$
What are the units of $K_{D}$?
Units are concentration
What does does a $K_{D}$ of X units mean?
Concentration at which the protein is half-saturated with ligand.
We can measure $K_{D}$ by following $\theta$ versus $[L]$
$K_{D} = \frac{[M][L]}{[ML]}$
$[ML] \times K_{D} = [M][L]$
$[ML] = \frac{[M][L]}{K_{D}}$
$\theta = \frac{[ML]}{[M] + [ML]}$
$\theta = \frac{[M][L]/K_{D}}{[M] + [M][L]/K_{D}}$
$\theta = \frac{[L]/K_{D}}{1 + [L]/K_{D}}$
$\theta = \frac{1}{1 + K_{D}/[L]}$
What determines affinity?
Loss of a hydrogen bond goes a long way towards explaining the specificity against testosterone