High-resolution structure of a Kazal-type serine protease inhibitor from the dengue vectorAedes aegypti

Abstract

Blood-feeding exoparasites are rich sources of protease inhibitors, and the mosquitoAedes aegypti, which is a vector ofDengue virus,Yellow fever virus,Chikungunya virusandZika virus, is no exception. AaTI is a single-domain, noncanonical Kazal-type serine proteinase inhibitor fromA. aegyptithat recognizes both digestive trypsin-like serine proteinases and the central protease in blood clotting, thrombin, albeit with an affinity that is three orders of magnitude lower. Here, the 1.4 Å resolution crystal structure of AaTI is reported from extremely tightly packed crystals (∼22% solvent content), revealing the structural determinants for the observed inhibitory profile of this molecule.