aspartatproteaser

Aspartatproteaser, also known as aspartic protease, refers to a family of proteolytic enzymes that use two aspartate residues in their active site to hydrolyze peptide bonds. They are found in many organisms and play roles in digestion, protein turnover, and regulation of peptide hormones. Notable members include pepsin and pepsinogen in the stomach, cathepsin D and cathepsin E in lysosomes, renin in blood pressure regulation, and the HIV-1 protease essential for viral maturation. Some aspartic proteases are synthesized as inactive precursors (zymogens) that require proteolytic activation.

The catalytic mechanism involves a pair of aspartate residues forming a catalytic dyad within a two-domain structure. In the active site, one aspartate acts as a general base to activate a water molecule, while the other stabilizes the transition state of the peptide bond being cleaved. This mechanism allows aspartic proteases to cleave peptide bonds with broad specificity, often favoring hydrophobic or uncharged residues near the scissile bond. The active site typically contains conserved motifs, such as DTG sequences in each lobe, characteristic of many members of this family.

Physiological and clinical relevance varies by member. Pepsin operates optimally at acidic pH in the stomach, facilitating digestion of dietary proteins. Cathepsins D and E function in acidic lysosomal compartments, contributing to intracellular protein degradation. HIV-1 protease is a target for antiretroviral therapy; its inhibition prevents maturation of infectious virions. Inhibitors of other aspartic proteases are explored for therapeutic and industrial applications, reflecting the diverse roles of this enzyme class.