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Publication Abstract from PubMed

Angiotensin-1 converting enzyme (ACE) is a key enzyme in the renin-angiotensin-aldosterone and kinin systems where it cleaves angiotensin I and bradykinin peptides, respectively. However, ACE also participates in numerous other physiological functions, can hydrolyse many peptide substrates, and has various exo- and endopeptidase activities. ACE achieves this complexity by containing two homologous catalytic domains (N- and C-domains), which exhibit different substrate specificities. Here we present the first open conformation structures of ACE N-domain, and a unique closed C-domain structure (2.0 A) where the C-terminus of a symmetry-related molecule is observed inserted into the active site cavity and binding to the zinc ion. The open native N-domain structure (1.85 A) enables comparison with ACE2, a homologue previously observed in open and closed states. An open S2 _S'-mutant N-domain structure (2.80 A) includes mutated residues in the S2 - and S'- subsites that effect ligand binding, but are distal to the binding site. Analysis of these structures provides important insights into how structural features of the ACE domains are able to accommodate the wide variety of substrates and allow different peptidase activities.

Angiotensin-converting enzyme open for business: structural insights into the sub-domain dynamics.,Cozier GE, Lubbe L, Sturrock ED, Acharya KR FEBS J. 2020 Oct 17. doi: 10.1111/febs.15601. PMID:33067882^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.