Molecular Recognition and Regulation of Human Angiotensin-I Converting Enzyme (ACE) Activity by Natural Inhibitory Peptides

Overview

Journal Sci Rep

Specialty Science

Date 2012 Oct 12

PMID 23056909

Citations 56

Authors

Geoffrey Masuyer

Sylva L U Schwager

Edward D Sturrock

R Elwyn Isaac

K Ravi Acharya

Affiliations

Soon will be listed here.

Abstract

Angiotensin-I converting enzyme (ACE), a two-domain dipeptidylcarboxypeptidase, is a key regulator of blood pressure as a result of its critical role in the renin-angiotensin-aldosterone and kallikrein-kinin systems. Hence it is an important drug target in the treatment of cardiovascular diseases. ACE is primarily known for its ability to cleave angiotensin I (Ang I) to the vasoactive octapeptide angiotensin II (Ang II), but is also able to cleave a number of other substrates including the vasodilator bradykinin and N-acetyl-Ser-Asp-Lys-Pro (Ac-SDKP), a physiological modulator of hematopoiesis. For the first time we provide a detailed biochemical and structural basis for the domain selectivity of the natural peptide inhibitors of ACE, bradykinin potentiating peptide b and Ang II. Moreover, Ang II showed selective competitive inhibition of the carboxy-terminal domain of human somatic ACE providing evidence for a regulatory role in the human renin-angiotensin system (RAS).

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