The initial substrate-binding site of -secretase is located on presenilin near the active site

Functional Plasticity in the Substrate Binding Site of -Secretase

The aspartic protease -secretase (BACE) cleaves the amyloid precursor protein into a 42 residue -peptide, which is the principal biochemical marker of Alzheimer’s disease. Multiple explicit-water molecular dynamics simulations of the apo and inhibitor bound structures of BACE indicate that both openand closed-flap conformations are accessible at room temperature and should be taken into account...

Podoplanin is a substrate of presenilin-1/γ-secretase.

Podoplanin (PDPN) is a mucin-like transmembrane glycoprotein that plays an important role in development and cancer. Here, we provide evidence that the intracellular domain (ICD) of podoplanin is released into the cytosol following a sequential proteolytic processing by a metalloprotease and γ-secretase. Western blotting and cell fractionation studies revealed that HEK293T and MDCK cells transf...

The substrate binding site of pepsin.

In earlier reports from this laboratory, a series of new synthetic substrates for pepsin was described.'-' These compounds are of the general type Z-His-X-YOAI\e4 where X and Y are the residues of amino acids such as L-phenylalanine, p-nitro-L-phenylalanine, L-tyrosine, L-tryptophan, and L-leucine; the enzymic action is limited to the cleavage of the X-Y bond. One of the substrate analogues pre...

Substrate interactions with the nitrogenase active site.

The chemical mechanism for biological cleavage of the N(2) triple bond at ambient pressure and temperature has been the subject of intense study for many years. The site of substrate activation and reduction has been localized to a complex cofactor, called FeMo cofactor, yet until now the complexity of the system has denied information concerning exactly where and how substrates interact with t...

PROBING THE ACTIVE SITE OF RHODANESE WITH DISULFIDE REAGENTS