Lecture 8 Flashcards
Where does enzyme - substrate binding occur?
At the active site
What is the structure of an active site?
Has several amino acid side chains projecting into it that create binding specificity
How does the active site bind substrate?
Via several weak interactions with amino acid residues
What is the equation for the reaction of substrate and enzyme?
E + S ⇌ ES ⇌ EX‡ → EP
Why are Enzyme-substrate bonds weak but numerous?
To ensure specificity and reversibility
What is molecular complementarity in terms of enzymes?
When enzyme and substrate have complementary atoms/functional groups that bind precisely to one another in the active site
Why are weak bonds advantageous?
Can only form if the relevant atoms are precisely positioned and they are easy to break
What are types of enzyme-substrate bond?
Ionic bonds, hydrogen bonds, van der waals interactions, covalent bonds
What are ionic enzyme-substrate bonds?
Attractions between charged (protonated/deprotonated) amino acid side chains
What are hydrogen enzyme-substrate bonds?
H-bonds between side chain or backbone O and N atoms of amino acids
What are enzyme-substrate van der Waals interactions?
Interactions between any protein and substrate atoms in close proximity
What is the weakest type of chemical bond?
Van der Waals/dispersion forces
What are covalent enzyme-substrate bonds?
A rare type of strong bond between atoms of the substrate and protein atoms
How are active sites stereospecific?
If the active sites are asymmetric, they can distinguish between stereoisomers (D or L)
What are the two types of enzyme-substrate binding models?
Lock and Key and Induced fit
What is the lock and key model?
The shape of the substrate and the conformation of the active site are complementary to one another
What is the induced fit model?
The enzyme undergoes a conformational change upon binding to the substrate. The shape of the active site becomes complementary to the shape of the substrate only after binding to the enzyme
Are enzymes dynamic or static?
Dynamic
How is ∆G‡ lowered?
Ground state destabilisation, transition state stabilisation and alternate reaction pathway with a lower energy transition state
What are the five catalytic mechanisms
Preferential binding of the transition state, proximity and orientation effects, Acid-base catalysis, metal ion catalysis, covalent catalysis
What is the prediction of preferential binding of the transition state?
An enzyme should bind the transition state more tightly than it binds the substrate
What is the problem of preferential binding of the transition state?
Transition states are transient and cannot be isolated -> need to design and synthesise an analogue
What are transition state analogues as drugs?
Enzymes are often targets for drugs and other beneficial agents, analogues often make ideal enzyme inhibitors
What is the function of enalapril and aliskiren?
To lower blood pressure
