Molecular recognition and regulation of human angiotensin-I converting enzyme (ACE) activity by natural inhibitory peptides

Sci Rep. 2012;2:717. doi: 10.1038/srep00717. Epub 2012 Oct 9.

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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism*
  • Angiotensin-Converting Enzyme Inhibitors / metabolism*
  • Crystallography, X-Ray
  • Humans
  • Oligopeptides / metabolism*
  • Peptidyl-Dipeptidase A / chemistry*
  • Peptidyl-Dipeptidase A / metabolism*
  • Protein Structure, Tertiary
  • Renin-Angiotensin System

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Oligopeptides
  • bradykinin potentiating factors
  • Angiotensin II
  • ACE protein, human
  • Peptidyl-Dipeptidase A