Michael Cusack

May 4th, 2009

BME220


HW2: Making Pictures
STRUCTURE OF A SERPIN:PROTEASE COMPLEX (1EZX)

Figure 1: Activated Antitrypsin (Red) Disrupts Trypsin Protease (Green)
Figure 1: Activated Antitrypsin (Red) Disrupts Trypsin Protease (Green) Figure 2: Close-up of Top Right Corner of Figure 1
Figure 2: Close-up of Top Right Corner of Figure 1

Trypsin is an important protease enzyme used for digestion in mammals and several other vertebrates. It breaks down proteins by cleaving them at the carboxyl side of lysine and arginine residues. To regulate and counteract this action produce Alpha 1-Antitrypsin. Antitrypsin and other serpins (serine protease inhibitors) are often found in high concentrations in the blood, and other places where random protein cleavage would be undesirable. Unactivated Antitrypsin (shows in red) contains an cleavage site which is normally targeted by Trypsin (shown in green). Upon cleavage half of the Antitrypsin polypeptide (show as red sticks in figure 1) leaves and becomes disattached. Figure 3 shows unattached half of Antitrypsin lingering beside the Trypsin molecule.

Figure 3: Shows the disattached, yet lingering, cleaved portion of Antitrypsin (red) near the side of Trypsin (green) opposite of active site

The remaining now active portion of Antitrypsin (shown prominently as red balls in figure 2) binds tightly with the Trypsin molecule, thereby preventing it from attacking another protein and deactivating it. The "arm" of Trypsin which is unable to detach and release the fragment as it normally would is shown as green sticks.