Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.698952
Title: Structure based inhibitor design studies on angiotensin converting enzyme homologues
Author: Harrison, Charlotte
ISNI:       0000 0004 5993 5580
Awarding Body: University of Bath
Current Institution: University of Bath
Date of Award: 2015
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Abstract:
Angiotensin converting enzyme, ACE (EC number 3. 4. 15. 1), is a zinc dependent dipeptidyl carboxypeptidase that has an essential role in mammalian blood pressure regulation as part of the renin-angiotensin aldosterone system. ACE acts to increase blood pressure through its actions on two peptides: angiotensin I and bradykinin. In light of this role ACE is a key target in the treatment of hypertension and ACE inhibitors have been widely used since the 1980s. Although these are effective drugs, a number of side effects are commonly associated with their use. These occur as a result of the inhibition of the roles of ACE in other physiological processes. Somatic ACE consists of two homologous domains, each with a functional peptidase active site. Only one of these domains, the C-domain, is required for blood pressure homeostasis. There is a great deal of interest in developing a new generation of ACE inhibitors to selectively target the C-domain, whilst leaving the N-domain active and able to fulfil the other biological functions of ACE. In the work presented here, AnCE, an ACE homologue from Drosophila melanogaster, has been used as a model to study the structural basis of ACE inhibition by a number of different inhibitory peptides. This has highlighted how interactions with active site residues could be exploited in the development of new, domain selective, inhibitors. ACE homologues in insects are thought to have a conserved role in reproduction. The ACE-like enzymes from Anopheles gambiae are of particular interest due to the role of this organism in the transmission of malaria. In the work presented here the recombinant expression of an ACE homologue from Anopheles gambiae is reported for the first time. This is an important step towards the structural and biochemical characterisation of these enzymes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.698952  DOI: Not available
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