Cathepsin L from human liver

The cathepsin L (CTSL) gene is mapped to human chromosome 9q21.33. It encodes a lysosomal cysteine proteinase that belongs to the peptidase C1 family. The enzyme is a dimer of a heavy (175 amino acids) and a light chain (42 amino acids) linked by disulfide bonds.

Cathepsin L (CTSL) from human liver has been used:

• to digest mutant transforming growth factor β-induced (TGFBIp) and LC3 (autophagosomes marker) proteins in vitro
• to digest the pH-dependent fibril of a pre-melanosomal protein (Pmel17) repeat domain (RPT) isoform and study the effect of pH on sRPT aggregation kinetics by tryptophan fluorescence
• to analyze the inhibition of CTSL by small molecules or drugs in a cell-free system

Cathepsin L (CTSL) exhibits endopeptidase activity and breaks peptide bonds with aromatic residues. This enzyme is functional at pH 3.0–6.5 with thiol compounds. Elastin, collagen, and α-1 protease inhibitors act as substrates for cathepsin L (CTSL). CTSL cleaves several proteins including enzymes, receptors, and transcription factors. It is involved in antigenic peptide production and controls B-cells homeostasis. It is associated with myofibril necrosis and tumor progression. Increased expression of CTSL promotes metastasis and relates to poor prognosis in cancer patients. Increased expression of CTSL is observed in breast cancer. CTSL is implicated in glioblastoma multiforme (GBM), middle east respiratory syndrome (MERS), gingival overgrowth, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has a higher specific activity than cathepsin B and H in the degradation of a variety of physiological protein substrates.

Solution in in 20 mM malonate, pH 5.5, 1 mM EDTA, and 400 mM NaCl.

One unit will hydrolyze 1.0 μmole of Z-Phe-Arg-AFC per minute at pH 5.5 at 25 °C.