The
catalytic mechanism proposed by John Northrop involves a series of
steps where the acidic amino acids Aspartate - 215 and Aspartate - 32
activate a water molecule that is used to cleave protein chains (Dunn
2002).
The seven step catalytic mechanism for pepsin is illustrated below and surrounds a structural illustration of pepsin with Aspartate - 32 and Aspartate - 215 highlighted in yellow and the activated water molecule highlighted in red.
The seven step catalytic mechanism for pepsin is illustrated below and surrounds a structural illustration of pepsin with Aspartate - 32 and Aspartate - 215 highlighted in yellow and the activated water molecule highlighted in red.
The first step illustrates the active site of pepsin with Aspartate - 32 and Aspartate - 215 poised for catalysis. In the second step, Aspartate - 215 acts as a general base and removes a proton from the water molecule. This removal of a proton from water stimulates the attack of oxygen in step 3 on the carbonyl carbon of the incoming protein. In step 4, hydrogen is transferred to the nitrogen of the scissile bond. This sets up a bond cleavage event where the protein in cleaved into two products in steps 5 and 6. Aspartate - 215 loses a proton and a new water molecule reforms a low-barrier hydrogen bond between Aspartate - 215 and Aspartate - 32 in step 7 so that the catalytic mechanism can be repeated and a new protein chain can be cleaved (Dunn 2002).