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B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction
Takafumi Minato1, Satoru Nirasawa2, Teruki Sato1,3
1Department of Biochemistry and Metabolic Science, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
Nature Communications
|February 28, 2020
Summary
A bacterial enzyme, B38-CAP, mimics human Angiotensin-converting enzyme 2 (ACE2) activity. This enzyme effectively lowers angiotensin II levels, reducing hypertension and cardiac issues in mice, offering potential for new cardiovascular drug development.
Area of Science:
- Biochemistry
- Cardiovascular Physiology
- Enzymology
Background:
- Angiotensin-converting enzyme 2 (ACE2) plays a crucial role in cardiovascular function and disease.
- ACE2 is being investigated for treating acute lung failure.
- Understanding ACE2's function can lead to novel therapeutic strategies.
Purpose of the Study:
- To investigate the functional and structural similarity of bacterial carboxypeptidase B38-CAP to human ACE2.
- To evaluate the therapeutic potential of B38-CAP in cardiovascular conditions.
Main Methods:
- Protein 3D structure analysis to assess homology between B38-CAP and ACE2.
- In vitro enzymatic assays to determine B38-CAP's substrate specificity.
- In vivo studies in mice to assess the effects of B38-CAP on angiotensin II-induced and pressure overload-induced cardiovascular pathologies.
Main Results:
- B38-CAP exhibits structural similarity to human ACE2 despite low sequence identity.
- Recombinant B38-CAP effectively converts angiotensin II to angiotensin 1-7 and other ACE2 substrates in vitro.
- B38-CAP treatment ameliorated angiotensin II-induced hypertension, cardiac hypertrophy, and fibrosis in mice.
- B38-CAP administration inhibited pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction in response to pressure overload.
Conclusions:
- Bacterial B38-CAP functions as an ACE2-like carboxypeptidase, demonstrating convergent evolution.
- B38-CAP effectively reduces cardiovascular pathologies driven by the renin-angiotensin system.
- Bacterial engineering of enzymes like B38-CAP holds promise for developing novel protein-based therapeutics for hypertension and heart failure.
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