Conserved Interactions of the Active Carboxyls in Pepsin-like Enzymes and Retroviral Proteases

Abstract

In addition to previous studies, 30 crystal structures of retroviral proteases corresponding to the highest resolution were inspected to analyze the interactions of the active carboxyls with surroundings groups. The outer oxygens of the active carboxyls in retroviral enzymes form contacts only with the water molecule participating in catalysis. This is an important difference between retroviral proteases and pepsin-like enzymes, which form a net of hydrogen bonds of these outer oxygens with residues neighboring the catalytic site in 3D structures. At the same time, it was found that in all aspartic proteases the inner oxygens of the active carboxyls are also involved in the chain of interactions through peptide groups Thr–Gly adjacent to the active residues. Polarization of these peptide groups influences the donor–acceptor properties of the active carboxyls. The found chain of interactions is more extensive in retroviral than in pepsin-like proteases; however, its main part is conserved for the whole class of these enzymes. Some implications of the role of these interactions are discussed.