Internet Archive Scholar

B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction

Takafumi Minato, Satoru Nirasawa, Teruki Sato, Tomokazu Yamaguchi, Midori Hoshizaki, Tadakatsu Inagaki, Kazuhiko Nakahara, Tadashi Yoshihashi, Ryo Ozawa, Saki Yokota, Miyuki Natsui, Souichi Koyota (+10 others)
2020 Nature Communications  

Preserved Fulltext

fulltext thumbnail
Web Archive Capture PDF (2.2 MB)
https://web.archive.org/web/20200229040232/https://www.nature.com/articles/s41467-020-14867-z.pdf?error=cookies_not_supported&code=0b15058b-2e42-4006-acdc-10ac51901323

A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2020; you can also visit the original URL. The file type is application/pdf.

Angiotensin-converting enzyme 2 (ACE2) is critically involved in cardiovascular physiology and pathology, and is currently clinically evaluated to treat acute lung failure. Here we show that the B38-CAP, a carboxypeptidase derived from Paenibacillus sp. B38, is an ACE2-like enzyme to decrease angiotensin II levels in mice. In protein 3D structure analysis, B38-CAP homolog shares structural similarity to mammalian ACE2 with low sequence identity. In vitro, recombinant B38-CAP protein catalyzed
more » ... e conversion of angiotensin II to angiotensin 1-7, as well as other known ACE2 target peptides. Treatment with B38-CAP suppressed angiotensin II-induced hypertension, cardiac hypertrophy, and fibrosis in mice. Moreover, B38-CAP inhibited pressure overload-induced pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction in mice. Our data identify the bacterial B38-CAP as an ACE2-like carboxypeptidase, indicating that evolution has shaped a bacterial carboxypeptidase to a human ACE2-like enzyme. Bacterial engineering could be utilized to design improved protein drugs for hypertension and heart failure.
doi:10.1038/s41467-020-14867-z pmid:32103002 fatcat:llm5drjp6vbtbb434lscxpafhu
DOAJ
Citation

Takafumi Minato, Satoru Nirasawa, Teruki Sato, Tomokazu Yamaguchi, Midori Hoshizaki, Tadakatsu Inagaki, Kazuhiko Nakahara, Tadashi Yoshihashi, Ryo Ozawa, Saki Yokota, Miyuki Natsui, Souichi Koyota, Taku Yoshiya, Kumiko Yoshizawa-Kumagaye, Satoru Motoyama, Takeshi Gotoh, Yoshikazu Nakaoka, Josef M. Penninger, Hiroyuki Watanabe, Yumiko Imai, Saori Takahashi, Keiji Kuba. "B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction." Nature Communications 11.1 (2020) 1058