KAZAL TYPE PROTEASE INHIBITORS LEKTI AND KA69: STRUCTURE, FUNCTION AND IMPLICATION IN DISEASE

Abstract

Kazal type serine protease inhibitors are involved in regulating various biological process in living organisms. LEKTI is a 15-domain non-classical Kazal type inhibitor involved in the regulation of epidermal desquamation, which is essential for skin homoeostasis. Several point mutations occurring in LEKTI are associated with Atopic Dermatitis. In the current study, the effects of the exonic mutations in domain 4 and 6 on its inhibitory function and degradation rate are examined. In addition, their role in blood coagulation cascade was explored. Structural and dynamic studies are carried out to elucidate the mechanism of action of these LEKTI domains. The final part of the study is on KA69, a Kazal type inhibitor from Aedes aegypti, which is an active plasmin inhibitor. The effect of plasmin in enhancing vector competence for dengue viral transmission and the ability of KA69 to provide immunity against this infection in the mosquito is demonstrated in the study.