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Cryo-EM structure of angiotensin-converting enzyme: novel structural and mechanistic insights into cooperativity, dimerization and allostery

19 Aug 2024 (1:20 pm)

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19 Aug 2024 (2:00 pm)

Workshop Lecture or Event

angiotensin-converting enzyme, cryo-EM, hypertension

Part of:

Inside the Researcher’s Mindset Congress (2024)

Venue:

Institute of Infectious Disease & Molecular Medicine

Speaker:

Prof. Ed Sturrock

Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase that plays a critical role in blood pressure, and fluid and electrolyte homeostasis. ACE can cleave angiotensin I, bradykinin, and many other peptide substrates. Until recently, little was known regarding the specific role of each of the two ACE domains, their 3D structural orientation, dynamics and dimerization. In this talk I describe the first cryo-EM structures of full-length, glycosylated somatic ACE. Mechanisms are proposed for domain hinging, cooperativity, and homodimerization. Furthermore, the observation that both domains were in the open conformation has important implications for the design of allosteric modulators of ACE.