Pepsinogen and Pepsin

Evidence relating to the structure and properties of swine pepsinogen and pepsin has been reviewed and used to suggest a tentative two dimensional picture of the skeleton of these two proteins. When pepsinogen, a folded single peptide chain, is converted to pepsin, there is a profound change in the physical and chemical properties of the protein. In an as yet unknown manner, except that it is initiated by a peptic cleavage of the protein chain, a single enzymic site is formed. This site is made up, quite probably, of the secondary carboxyl group of glutamic acid or of aspartic acid and a tyrosine phenol group in close proximity so that they can form hydrogen or hydrophobic bonds with the substrate in some unique manner that permits hydrolysis to occur at an accelerated rate. I N T R O D U C T I O N Volumes have been written about the action of enzymes, bu t little is known which explains their catalytic action in chemical terms. This is particularly true of the hydrolytic enzymes which have no prosthetic groups or coenzymes. It is generally assumed that in these enzymes some tertiary structure (1) of the protein developed, perhaps, by the folding of the long peptide chain, is responsible for the enzymic property. Today, largely as a result of the ini~ence of Northrop's work, many highly purified enzymes, and in some instances, their precursors, are available for structural studies, and a number of laboratories are using a variety of means to uncover the explanation for enzyme catalysis. The work on ribonuclease (2-4), chymotrypsin and trypsin (5-I0) , papain (l l, 12), acetylcholinesterase (13), and fumerase (14) is leading the advance, yet in no case has the structure which binds the substrate been well established. A solution to these problems comes slowly, for unless one has the good fortune to be able to digest away most of the protein without loss of enzymic function, as was found for papain (l l), the approaches are indirect and the conclusions tentative. These indirect approaches are of many different types, not all of which have been applied to pepsin. A total amino acid sequence