The mechanism of action of aspartic proteases involves 'push-pull' catalysis.

In accord with the available kinetic and X-ray crystallographic data, it is proposed that the two catalytically competent carboxyl groups of aspartic proteases constitute a functional unit which mediates the proton from the attacking water molecule to the leaving nitrogen atom of the substrate. Protonation of this nitrogen atom has been the main issue of the previous mechanistic proposals. The first step of the present mechanism involves proton transfer from the water to the aspartic diad and concurrently another proton transfer from the diad to the carbonyl oxygen of the scissile peptide bond. These proton transfers provide the driving force for the bond formation between the substrate and water, which leads to the formation of a tetrahedral intermediate. The intermediate breaks down to products by a similar facilitation, i.e. by concerted general acid-base catalysis, which involves simultaneous proton transfers from the intermediate to the diad and from the diad to the leaving nitrogen of the substrate. The symmetrical mechanism of the formation and decomposition of the tetrahedral adduct resembles that found in the serine protease catalysis.