The selectivity of cathepsin D, a mammalian intracellular aspartyl proteinase involved in the degradation of endocytosed proteins, was studied. For this purpose, several proteins of known primary structure were subjected to mild proteolysis by the enzyme, and the preferentially cleaved peptide bonds were identified. Comparison of the primary structures around these sites indicates that cathepsi...

Although the echinocandin caspofungin primarily inhibits the synthesis of cell wall 1,3-beta-D-glucan, its fungicidal activity could also potentially perturb the expression of virulence factors involved in the ability of Candida albicans to cause infection. Expression of the C. albicans secretory aspartyl proteinase (SAP) and phospholipase B (PLB) virulence genes was determined by reverse trans...

Alzheimer's disease is a neurodegenerative condition characterized by an accumulation of toxic amyloid beta- (Aβ-)peptides in the brain causing progressive neuronal death. Aβ-peptides are produced by aspartyl proteinase-mediated cleavage of the larger amyloid precursor protein (APP). In contrast to this detrimental "amyloidogenic" form of proteolysis, a range of zinc metalloproteinases can proc...

Three dominant proteins (41, 48, and 49 kDa) were detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) in purified preparations of the extracellular aspartyl proteinase (AP) of Candida albicans. All three proteins bound to the specific carboxyl proteinase ligand, pepstatin A, and were associated with maximum AP activity. The N-terminal amino acid sequence for the 48-...

The effects of therapeutically relevant concentrations of the human immunodeficiency virus (HIV) proteinase inhibitors saquinavir and indinavir on the in vitro proteinase activity of Candida albicans were investigated with isolates from HIV-infected and uninfected patients with oral candidiasis. After exposure to the HIV proteinase inhibitors, proteinase activity was significantly reduced in a ...

The newly emerging astacin metalloproteinase family comprises multiple members with diverse functions. Most recently, the development-related functions have been attributed to both (1) proteolytic cleavage and subsequent release of active TGF-beta-like growth factors from latent inhibitory complexes and (2) modification of extracellular matrix (ECM) assembly and composition. We previously ident...