Enzyme Mechanisms - Serine Proteases
Part II
Part II. Serine Proteases - Comparison of Amino Acid Sequences.
To understand this process let's look at an example. Trypsin is a member of a family of enzymes known as the serine-proteases. Chymotrypsin and Elastase are also members of this family of enzymes. Trypsin, Chymotrypsin, and Elastase are synthesized in the pancreas and excreted into the intestine. They are made as pre-enzymes and activated in the intestine by partial proteolytic degradation. The AA sequences are very similar with 62 AA the same out of 257. Their 3-D structures are very similar - little alpha-helix - and a central beta sheet.
Figure 7. Comparison of the amino acid sequences of: A) trypsin; B) chymotrypsin; and C) elastase. The amino acids in common and their positions in the sequence are shown by colored highlighting. Three key amino acids (His-57, Asp-102 and Ser-195) involved in the mechanism of catalysis of these enzymes are emphasized by the large circles over them.
Figure from Principles of Biochemistry Zubay et al. copyright ©1995 by Wm. C. Brown Communications, Inc.
Figure 8. Comparison of the 3-D structures of tryspin, chymotrypsin and elastase. The 3-D structures are overlaid one on another with the ribbon of each backbone shown in a different color: trypsin in green, chymotrypsin in yellow and elastase in pink. The active site is shown at the middle of the 3-D composite and the key amino acid side chains are shown projecting into the active site (His-57 in blue, Asp-102 in red and Ser-195 in orange with its reactive oxygen in red). It is clear that these 3-D structures for the 3 enzymes are very similar. The thin lines in each sequence represent disulfide bonds which cross-link the polypeptide backbone of each enzyme. In trypsin and chymotrypsin, the sections of the amino acid sequences removed by proteolytic degradation during activation in the intestine are shown by '+++'. Thus, part of the function of the disulfide bonds is to help anchor these cleaved sections of the enzyme to the main 3-D structure.
Figure from Principles of Biochemistry Zubay et al. copyright ©1995 by Wm. C. Brown Communications, Inc.
©Wilbur H. Campbell, 1995; wcampbel@mtu.edu