Angiotensin-I converting enzyme (ACE): Structure, biological roles, and molecular basis for chloride ion dependence

Geoffrey Masuyer, Christopher J. Yates, Edward D. Sturrock, K. Ravi Acharya

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Somatic angiotensin-I converting enzyme (sACE) has an essential role in the regulation of blood pressure and electrolyte fluid homeostasis. It is a zinc protease that cleaves angiotensin-I (AngI), bradykinin, and a broad range of other signalling peptides. The enzyme activity is provided by two homologous domains (N- and C-), which display clear differences in substrate specificities and chloride activation. The presence of chloride ions in sACE and its unusual role in activity was identified early on in the characterisation of the enzyme. The molecular mechanisms of chloride activation have been investigated thoroughly through mutagenesis studies and shown to be substrate-dependent. Recent results from X-ray crystallography structural analysis have provided the basis for the intricate interactions between ACE, its substrate and chloride ions. Here we describe the role of chloride ions in human ACE and its physiological consequences. Insights into the chloride activation of the N- and C-domains could impact the design of improved domain-specific ACE inhibitors.

Original languageEnglish
Pages (from-to)1135-1149
Number of pages15
JournalBiological Chemistry
Volume395
Issue number10
DOIs
Publication statusPublished - 1 Oct 2014

Keywords

  • Angiotensin-I converting enzyme
  • Chloride activation
  • Hypertension

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Medicine(all)

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