Enzymes catalyze reactions by stabilizing the transition state. The enzyme's active site provides a catalytic surface that lowers the energy needed for the reaction to proceed. Specific amino acids and cofactors in the deep buried active site pocket recognize and fit the transition state, shielding it from water and allowing reactive groups to form stable bonds to reduce the energy of activation.

1. Stickase
Substrate
Transition state Product
X
If enzyme just binds substrate
then there will be no further reaction
Enzyme not only recognizes substrate,
but also induces the formation of transition state
Adapted from Nelson & Cox (2000) Lehninger Principles of Biochemistry (3e) p.252

2. The Nature of Enzyme Catalysis
● Enzyme provides a catalytic surface
● This surface stabilizes transition state
● Transformed transition state to product
B
A
A B Catalytic surface
Juang RH (2004) BCbasics

3. Enzyme Stabilizes Transition State
Energy change
ST
Energy required (no catalysis)
Energy decreases (under catalysis)
EST
S
ES
EP P
Reaction direction
T = Transition state What’s the difference?
Adapted from Alberts et al (2002) Molecular Biology of the Cell (4e) p.166

4. Active Site Is a Deep Buried Pocket
Why energy required to reach transition state
is lower in the active site?
It is a magic pocket
+ (1) Stabilizes transition
(2) Expels water
CoE (1) (2)
(3) Reactive groups
(4) - (4) Coenzyme helps
(3)
Juang RH (2004) BCbasics

5. Enzyme Active Site Is Deeper than Ab Binding
Instead, active site on enzyme
also recognizes substrate, but
Ag binding site on Ab binds to Ag
actually complementally fits the
complementally, no further reaction
transition state and stabilized it.
occurs.
X
Adapted from Nelson & Cox (2000) Lehninger Principles of Biochemistry (3e) p.252

6. Active Site Avoids the Influence of Water
+
-
Preventing the influence of water sustains the formation of stable ionic bonds
Adapted from Alberts et al (2002) Molecular Biology of the Cell (4e) p.115

7. Active Site Avoids the Influence of Water
+
-
Preventing the influence of water sustains the formation of stable ionic bonds
Adapted from Alberts et al (2002) Molecular Biology of the Cell (4e) p.115