aspartaatproteaasid

Aspartaatproteaasid, also known as aspartic proteases, are a class of proteolytic enzymes that use a pair of aspartate residues in their active site to catalyze the hydrolysis of peptide bonds. They are distinct from serine, cysteine, and metalloproteases in that the catalytic mechanism relies on the deprotonation of a water molecule by the aspartate side chains, which then attacks the carbonyl carbon of the substrate peptide. This mechanism is similar to that of the proteasome, allowing aspartase to cleave a broad range of peptide sequences, though their substrate specificity can vary greatly between members.

The typical aspartate protease fold is a bilobal structure consisting of two nearly symmetrical domains connected by a hinge region. Each domain contributes one of the catalytic aspartate residues, usually positioned in a conserved motif –DTG– located in an aspartic corner of the β-sheet. Many aspartaatproteaasid are synthesized as inactive zymogens; activation requires proteolytic cleavage that exposes the catalytic dyad. Examples include pepsin A, renin, and HIV-1 protease. In humans, pepsin is involved primarily in gastric protein digestion, whereas renin regulates blood pressure by cleaving angiotensinogen to produce angiotensin I. The viral protease of HIV is essential for processing the polyprotein Precursors and is a major target of antiretroviral drugs, such as inhibitors that resemble transition-state analogues.

Aspartate proteases are found across all domains of life, including bacteria, fungi, and vertebrates. They play roles in protein maturation, degradation of extracellular matrix, activation of bacterial toxins, and regulation of hormone processing. The high conservation of the active-site motif makes them attractive targets for drug design and inhibitor development. In industrial applications, aspartate proteases are used for protein modification in the food, detergent, and textile industries due to their robust activity over a range of conditions.