The difference between the structures of tyrpsinogen and trypsin is small:

• Just the loss of six amino acids from one end

• The overall structures remain similar; the backbones superpose with an rmsd of 0.59 A:
  

• However, the activated enzyme does have more of its structure organized into sheets. (The violet ball is a Ca⁺⁺, which helps to provide thermal stability.)

  Trypsinogen (1tgb)	Trypsin (5ptp)

The change from chymotrypsinogen to chymotrypsin is more profound

• The chain is clipped in four places: between residues 13 and 14; 15 and 16; 146 and 147, and 148 and 149.

• This results in release of two dipeptides, and the creation of two breaks in the backbone.

• However, the 1-13 segment is retained as part of the active enzyme, linked on by a disulfide bond

• Chymotrypsin and elastase are the only proteases that retain the "activation segment"

Chymotrypsinogen (2cga)	Chymotrypsinogen (2cga), Deleted Dipeptides Highlighted
Chymotrypsin (1acb)	Chymotrypsin: Three Pieces and Two Disulfides

The two disulfide bonds that hold the chymotrypsin together are Cys1-Cys122 and Cys136-201.

The backbones superpose with an rmsd of 0.74 A:

The gray-blue chain is the zymogen, and chymotrypsin itself is the green chain. The crucial difference between the two structures is the absence of a substrate binding pocket in the zymogen.

The residues shown in yellow are the ones that develop the pocket.

• Ile16 has just become the new N-terminal, producing an NH₃⁺ that turns inward and interacts with the side-chain carboxyl of Asp194, forming an ion pair. This opens up the binding pocket.

• The three residues shown in red are the catalytic groups, Asp102, His57, and Ser195 (about which much more later).

Here are two separate pictures that show more clearly the structural change that accompanies the formation of the ion pair:

Chymotrypsinogen (2cga)	Chymotrypsin (1acb)

In the zymogen, the residue in red at the bottom is Ile16; the other red one is Asp194.

His57, Asp102, and Ser195 are colored in CPK colors to locate the active site. You can see looking at the enzyme itself that Ile16 has folded up toward Asp194.

Closeups:

Chymotrypsinogen (2cga)	Chymotrypsin (1acb)

The effect of the change is to turn Asp194 outward, opening up the binding pocket. The catalytic site is essentially unchanged.

• Chymotrypsinogen will catalyze hydrolysis of small esters and peptides. indicating that the binding pocket is only partly blocked