What does cathepsin b cleave?
Cathepsin B is a cysteine protease that acts as an exopeptidase at pH<5.5 and as an endopeptidase at pH>5.5 [3]. Its cleavage specificity prefers, but is not restricted to, basic amino acids at the P1 position and hydrophobic or arginine residues at the P2 position [24].
What does cathepsin B do?
Structurally, cathepsin B is a bilobal protein with cysteine, histidine, and aspartic acid forming active site of the enzyme at the interface between the two lobes [37]. Cathepsin B can function as an endopeptidase, cleaving internal peptide bonds, as well as an exopeptidase (carboxydipeptidase activity) [37, 38].
Where does cathepsin b cleave?
lysosomes
Cathepsin B is a lysosomal protease that is expressed almost exclusively in all mammalian lysosomes and is found to be overexpressed in many cancer cells.
What is cysteine cathepsin?
In addition to the aspartic cathepsin D, cysteine cathepsins have a key role among the lysosomal proteases. They belong to the clan CA of cysteine peptidases, which are widely distributed among living organisms, and represent one of the most investigated groups of enzymes.
How is active site mapping of cathepsin B performed?
In case of chromogenic or fluorogenic peptidic substrates, the kinetic parameters of substrate consumption have been used to perform active site mappings of cathepsin B.
What are the specificity pockets of cathepsin B?
The specificity pockets S3, S2, S1, S1′ and S2′ are formed by loops of the left (S3, S1, S2′) or right (S2, S1′) domain.5, 6, 8 Cathepsin B shows both endopeptidase and exopeptidase activity (Fig. 1). In the open conformation, large endopeptidase substrates can be bound and cleaved.
How are cathepsin B inhibitors used in medicine?
The development of potent and selective low-molecular cathepsin B inhibitors relies on the detailed expertise on preferred amino acid and inhibitor residues interacting with the corresponding specificity pockets of cathepsin B.
What is the potential of cathepsin B protease?
The potential of papain-like cysteine proteases, such as cathepsin B, as drug discovery targets for systemic human diseases has prevailed over the past years.
