aspartylproteases

Aspartylproteases are a class of enzymes that catalyze the hydrolysis of peptide bonds. They are characterized by the presence of two aspartate residues in their active site, which are essential for their catalytic activity. These aspartate residues are typically conserved across different aspartylproteases and play a crucial role in the enzyme's mechanism of action, often involving proton abstraction and nucleophilic attack.

The catalytic mechanism of aspartylproteases generally involves the activation of a water molecule by the aspartate residues, which then attacks the scissile peptide bond of the substrate. This process leads to the formation of a tetrahedral intermediate, which subsequently collapses to release the products of the reaction and regenerate the enzyme.

Aspartylproteases are found in a wide range of organisms, from bacteria and viruses to plants and animals. In humans, notable examples include pepsin, renin, and cathepsin D. Pepsin, secreted in the stomach, is crucial for the initial digestion of dietary proteins. Renin, produced by the kidneys, plays a key role in regulating blood pressure through the renin-angiotensin-aldosterone system. Cathepsin D, found in lysosomes, is involved in protein degradation and processing.

Dysfunction or dysregulation of aspartylproteases can be associated with various diseases. For instance, aberrant pepsin activity can contribute to gastroesophageal reflux disease. Inhibitors of renin have been developed as antihypertensive drugs. Altered cathepsin D levels are implicated in neurodegenerative disorders like Alzheimer's disease and in cancer. The diverse roles and significant biological impact of aspartylproteases make them important targets for therapeutic intervention.