Inhibitor
Non-
functional
active
site
Stabilized inactive
form
Inactive form
Oscillation
Activator
Active form
Stabilized active form
Regulatory
site (one
of four)
Allosteric enzyme
with four subunits
Active site
(one of four)
Slide 68
Cooperativity is a form of allosteric regulation that can amplify enzyme activity
In cooperativity, binding by a substrate to one active site stabilizes favorable conformational changes at all other subunits
Slide 69
Fig. 8-20b
(b) Cooperativity: another type of allosteric activation
Stabilized active
form
Substrate
Inactive form
Slide 70
Allosteric regulators are attractive drug candidates for enzyme regulation
Inhibition of proteolytic enzymes called caspases may help management of inappropriate inflammatory responses
Slide 71
Fig. 8-21
RESULTS
EXPERIMENT
Caspase 1
Active
site
SH
Known active form
Substrate
SH
Active form can
bind substrate
SH
Allosteric
binding site
Known inactive form
Allosteric
inhibitor
Hypothesis: allosteric
inhibitor locks enzyme
in inactive form
S–S
Caspase 1
Active form
Allosterically
inhibited form
Inhibitor
Inactive form
Slide 72
Fig. 8-21a
SH
Substrate
Hypothesis: allosteric
inhibitor locks enzyme
in inactive form
Active form can
bind substrate
S–S
SH
SH
Active
site
Caspase 1
Known active form
Known inactive form
Allosteric
binding site
Allosteric
inhibitor
EXPERIMENT
Slide 73
Fig. 8-21b
Caspase 1
RESULTS
Active form
Inhibitor
Allosterically
inhibited form
Inactive form
Slide 74
In feedback inhibition, the end product of a metabolic pathway shuts down the pathway
Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed
Slide 75
Fig. 8-22
Intermediate C
Feedback
inhibition
Isoleucine
used up by
cell
Enzyme 1
(threonine
deaminase)
End product