Cystatin M/E Is a High Affinity Inhibitor of Cathepsin V and Cathepsin L by a Reactive Site Distinct from the Legumain-binding Site
TLDR Cystatin M/E strongly inhibits cathepsin V and cathepsin L, important for skin formation.
The study demonstrated that human cystatin M/E is a high-affinity inhibitor of cathepsin V (CTSV) and cathepsin L (CTSL), with Ki values of 0.47 and 1.78 nM, respectively. Site-directed mutagenesis showed that specific mutations could selectively disrupt inhibition of either CTSV/CTSL or legumain. Immunohistochemistry revealed co-localization of cystatin M/E with CTSV and CTSL in human skin, suggesting their role in epidermal differentiation. CTSL was identified as the enzyme that processes and activates epidermal transglutaminase 3, highlighting its importance in skin formation.
