This text explains why amino-acid side chains are chemically reactive, how enzymes exploit that reactivity for catalysis, and how chemists deliberately modify proteins to study enzyme mechanisms, structure, and function.
There are three major themes:
Nucleophilic catalysis occurs when a nucleophile from the enzyme itself attacks an electrophilic center on the substrate, forming a covalent enzyme–substrate intermediate.
This is far more effective than direct attack by water because:
🧠 Classic example: peptide bond hydrolysis via a serine acyl-enzyme
⚠️ Highly reactive → frequently targeted by inhibitors
The text emphasizes why enzymes do not rely on water:
Result: dramatically enhanced reaction rates.
Amino-acid side chains can react with chemical reagents to form covalent bonds. These reactions are used to:
⚠️ But modification can also:
⚠️ Cysteine is usually the most reactive side chain
This table is central and exam-important.
The text describes several powerful applications:
These are often called reporter groups.
Chemical modification helps determine:
📌 Protein engineering has now replaced many of these methods, but the concepts remain foundational.
The most important reactive groups in proteins are nucleophiles.
These target:
Also noted:
The text introduces the hydrophobic constant (π):
pi = log left( rac{P}{P_0} ight)
Where:
Hydrophobicity controls:
These tables quantify:
📌 Used to:
Although only partially shown, the section emphasizes:
Proteins are chemically active molecules, not inert scaffolds.
Their function depends on:
Chemical modification experiments historically revealed how enzymes work — and modern mutagenesis confirms those principles.