Substrate Specificity: In addition to rate enhancements, enzymes exhibit significant substrate specificity:

• They catalyze reaction of either single substrates, or small groups of substrates that are closely related structurally

• Analysis of the enzyme structure usually provides clear, compelling reasons for the specificity.

• Consider the three peptidase enzymes, chymotrypsin, trypsin, and elastase.
  • All three catalyze hydrolysis of peptide bonds

  • As we shall see later, they have very similar structures

  • All three use a "catalytic triad" of histidine, aspartate, and serine to do their work.

  • However, each hydrolyzes a specific subset of peptide bonds

• Chymotrypsin cleaves proteins on the carbonyl side of aromatic residues

• Trypsin hydrolyzes at residues with positively charged side chains: arginine and lysine

• Elastase hydrolyzes chiefly fibrous proteins like elastin, which are rich in glycine and alanine, cleaving only at residues with small uncharged side chains

  Here is a cartoon of the active sites of the three enzymes:

  

• The chymotrypsin site is relatively large, and lined with lipophilic side chains, suitable for stabilizing interactions with aromatic rings.

• The trypsin site is similar, but at the bottom is an aspartate residue, the negative charge of which interacts with the positive side chains of arginine and lysine.

• The elastase site has side chains of valine and threonine projecting into it, sterically blocking binding of all residues except those with small side chains.

• The binding step is responsible for the substrate specificity

Reaction Specificity:Another kind of selectivity noted for enzymes is called "reaction specificity" meaning that enzymes rarely form products other than the specific ones they are designed to produce.

• In organic chemists' terms, yields are 100%; no molecules follow other than the intended reaction channel.

• For a living critter, this specificity avoids both waste of metabolic resources, and the formation of by-products that might be toxic.

I suggest four mechanisms for this selectivity; perhaps you can think of others:

• Only the functional groups that catalyze a single, specific reaction are present in the enzyme

• Only the correct transition state is stabilized

• Only the correct product is readily released from the enzyme; incorrect ones may be held for another try, or may occasionally result in a "dead" enzyme

• Losses of material during isolation do not occur; no product is left sticking to the flask, or spilled in the sink

Stereospecificity: To discuss the stereochemistry of enzyme reactions, we need to review briefly what we know about stereoisomerism. Here are some review pages: