Crystal structures of angiotensin converting enzyme from Anopheles gambiae in its native form and with a bound inhibitor.

Crystal structures of angiotensin converting enzyme from Anopheles gambiae in its native form and with a bound inhibitor. Biochem J. 2019 Nov 04;: Authors: Cashman JS, Cozier GE, Harrison C, Isaac RE, Acharya KR Abstract The mosquitoes of the Anopheles and Aedes genus are some of the most deadly insects to humans because of their effectiveness as vectors of malaria and a range of arboviruses, including yellow fever, dengue, chikungunya, West Nile and zika. The use of insecticides from different chemical classes is a key component of the integrated strategy against An. gambiae and Ae. aegypti, but the problem of insecticide resistance means that new compounds with different modes of action are urgently needed to replace chemicals that fail to control resistant mosquito populations. We have previously shown that feeding inhibitors of peptidyl dipeptidase A to both An. gambiae and Ae. aegypti mosquito larvae leads to stunted growth and mortality. However, these compounds were designed to inhibit the mammalian form of the enzyme (angiotensin converting enzyme, ACE) and hence can have lower potency and lack selectivity as inhibitors of the insect peptidase. Thus, for the development of inhibitors of practical value in killing mosquito larvae, it is important to design new compounds that are both potent and highly selective. Here we report the first structures of AnoACE2 from An. gambiae in its native form and with a bound human ACE inhibi...
Source: The Biochemical Journal - Category: Biochemistry Authors: Tags: Biochem J Source Type: research