Structural basis of peptide recognition by the angiotensin-1 converting enzyme homologue AnCE from Drosophila melanogaster

Mohd Akif, Geoffrey Masuyer, Richard J. Bingham, Edward D. Sturrock, R. Elwyn Isaac, K. Ravi Acharya

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Human somatic angiotensin-1 converting enzyme (ACE) is a zinc-dependent exopeptidase, that catalyses the conversion of the decapeptide angiotensin I to the octapeptide angiotensin II, by removing a C-terminal dipeptide. It is the principal component of the renin-angiotensin-aldosterone system that regulates blood pressure. Hence it is an important therapeutic target for the treatment of hypertension and cardiovascular disorders. Here, we report the structures of an ACE homologue from Drosophila melanogaster (AnCE; a proven structural model for the more complex human ACE) co-crystallized with mammalian peptide substrates (bradykinin, Thr6-bradykinin, angiotensin I and a snake venom peptide inhibitor, bradykinin-potentiating peptide-b). The structures determined at 2-Å resolution illustrate that both angiotensin II (the cleaved product of angiotensin I by AnCE) and bradykinin-potentiating peptide-b bind in an analogous fashion at the active site of AnCE, but also exhibit significant differences. In addition, the binding of Arg-Pro-Pro, the cleavage product of bradykinin and Thr6- bradykinin, provides additional detail of the general peptide binding in AnCE. Thus the new structures of AnCE complexes presented here improves our understanding of the binding of peptides and the mechanism by which peptides inhibit this family of enzymes.

Original languageEnglish
Pages (from-to)4525-4534
Number of pages10
JournalFEBS Journal
Volume279
Issue number24
DOIs
Publication statusPublished - Dec 2012

Fingerprint

Angiotensins
Peptidyl-Dipeptidase A
Drosophila melanogaster
Bradykinin
Peptides
Angiotensin I
Enzymes
arginyl-prolyl-proline
Angiotensin II
Exopeptidases
Snake Venoms
Dipeptides
Structural Models
Blood pressure
Renin-Angiotensin System
Aldosterone
Renin
Zinc
Catalytic Domain
Blood Pressure

Cite this

Akif, Mohd ; Masuyer, Geoffrey ; Bingham, Richard J. ; Sturrock, Edward D. ; Isaac, R. Elwyn ; Acharya, K. Ravi. / Structural basis of peptide recognition by the angiotensin-1 converting enzyme homologue AnCE from Drosophila melanogaster. In: FEBS Journal. 2012 ; Vol. 279, No. 24. pp. 4525-4534.
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Structural basis of peptide recognition by the angiotensin-1 converting enzyme homologue AnCE from Drosophila melanogaster. / Akif, Mohd; Masuyer, Geoffrey; Bingham, Richard J.; Sturrock, Edward D.; Isaac, R. Elwyn; Acharya, K. Ravi.

In: FEBS Journal, Vol. 279, No. 24, 12.2012, p. 4525-4534.

Research output: Contribution to journalArticle

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