B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction
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Published:2020-02-26
Issue:1
Volume:11
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Minato Takafumi, Nirasawa Satoru, Sato Teruki, Yamaguchi Tomokazu, Hoshizaki Midori, Inagaki Tadakatsu, Nakahara Kazuhiko, Yoshihashi Tadashi, Ozawa Ryo, Yokota Saki, Natsui Miyuki, Koyota Souichi, Yoshiya TakuORCID, Yoshizawa-Kumagaye Kumiko, Motoyama Satoru, Gotoh Takeshi, Nakaoka YoshikazuORCID, Penninger Josef M.ORCID, Watanabe Hiroyuki, Imai Yumiko, Takahashi SaoriORCID, Kuba KeijiORCID
Abstract
AbstractAngiotensin-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 the 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.
Funder
Takeda Science Foundation Uehara Memorial Foundation Daiichi Sankyo Foundation of Life Science MEXT | Japan Society for the Promotion of Science
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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