Dimerization and dynamics of angiotensin-I converting enzyme revealed by cryo-EM and MD simulations.

ABSTRACT: Angiotensin-I converting enzyme (ACE) regulates the levels of disparate bioactive peptides, notably converting angiotensin-I to angiotensin-II and degrading amyloid beta. ACE is a heavily glycosylated dimer, containing 4 analogous catalytic sites, and exists in membrane bound and soluble (sACE) forms. ACE inhibition is a frontline, FDA-approved, therapy for cardiovascular diseases yet is associated with significant side effects, including higher rates of lung cancer. To date, structural studies have been confined to individual domains or partially denatured cryo-EM structures. Here we report the cryo-EM structure of the glycosylated full sACE dimer. We resolved four structural states at 2.99 to 3.65 Å resolution which are primarily differentiated by varying degrees of solvent accessibility

SUBMITTER: Mancl JM 

PROVIDER: S-EPMC11760429 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature