Dimerization and dynamics of human 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 four 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 human sACE dimer. We resolved four structural states at 2.99 - 3.65 Å resolution which are primarily differentiated by varying degrees of solvent acce

SUBMITTER: Mancl JM 

PROVIDER: S-EPMC12459953 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature