Enzyme Mechanisms - Serine Proteases
Part I
Part I. Introduction - Concept of an Enzyme's Mechanism of Catalysis.
The concept of a mechanism of a reaction as used in organic chemistry was explained in the last lecture as an introduction for its use in biochemistry. In biochemistry the same thing is done to explain how an enzyme catalyzes a reaction. But the process is more complicated. Here the question raised at the end of the last lecture will be answered. These questions were: How do the amino acid side chains of an enzyme assist is bond rearrangements? Can a plausible mechanism of action for enzyme catalyzed reactions be formulated by the biochemist in a manner similar to that done by the organic chemist?
First, one must discover what amino acid (AA) side chains in the enzyme (protein) are involved in catalysis - so try to identify the active site of the enzyme. We know that only a few AAs will be at the active site, since most of the AAs are involved in forming the framework of the enzyme (protein). OK - so you determine the AA sequence of the enzyme. Assuming that there are similar enzymes catalyzing the same type of reaction, then determine the AA sequences of enzymes that catalyze the same type of reaction. Then compare those sequences to identify identical residues (AAs). These AA residues will have important side chains involved in the active site and in forming the framework. Let's approach this subject using proteases like trypsin, chymotrypsin etc., which are enzymes that you are already a bit familiar with. The mechanism of catalysis for these enzymes, which are called serine proteases since serine plays a key role in catalysis, is very well understood.
©Wilbur H. Campbell, 1995; wcampbel@mtu.edu