Structure and Enzyme Kinetics Studies on Different Forms of Cathepsin L: Implication on Development of Anticancer Agents

Cathepsin L (enzyme classification number: EC 3.4.22.15) belongs to the family of Cathepsins, which are proteases and share a conserved active site formed by cysteine and histidine residues. Cathepsin L is widely distributed in the cell; particularly, it is mainly located in lysosomes, in the nucleus and in extracellular compartment. Cathepsin L is responsible for different physiological processes, depending on its particular location. Indeed, cathepsins not only mediate terminal protein degradation in lysosomes, they also process and activate proteins including growth factors in extracellular environment and transcription factors in the nucleus. Consequently, they are involved in several pathological states, ranging from cancer and methastasis to inflammatory disorders. In this work, the kinetics of cathepsin L binding to its substrate Z-Phe-Arg-AMC was studied by modifying some environment parameters, in order to simulate various cellular compartments and explore how the kinetics of this enzyme may change in different biological conditions.