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Comment
. 2021 Apr 13;118(15):e2023648118.
doi: 10.1073/pnas.2023648118.

His345 mutant of angiotensin-converting enzyme 2 (ACE2) remains enzymatically active against angiotensin II

Pan Liu  1 , Xinfang Xie  1 , Li Gao  1 , Jing Jin  2
Affiliations
Comment

His345 mutant of angiotensin-converting enzyme 2 (ACE2) remains enzymatically active against angiotensin II

Pan Liu et al. Proc Natl Acad Sci U S A. .
No abstract available

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Figures

Fig. 1.
Fig. 1.
Substrate-dependent activities among ACE2 mutants. (A) Surrogate substrate Mca-APK-DNP is cleaved between P and K as compared to the P−F cleave site in Ang II by ACE2. (B) ACE2 activity assays were performed using either Mca-APK-DNP or Ang II as substrate, with individual variants of ACE2-Fc as the enzyme. H345A showed loss of activity toward the surrogate (Left; N.D. for not detected), in agreement with the findings by Glasgow et al. (1). However, ACE2-Fc enzymatic activity measured by Ang II showed different results, with H345A having full activity as compared to wild-type ACE2-Fc (Right). Meanwhile, R273A showed loss of activity against Ang II. (C) To further confirm the specificity of the reaction, we conducted mass spectrometry analysis of the peptide(s) generated from the reactions, using Ang II peptide as substrate, that further confirmed the loss of activity by R273A mutation, whereas H345A of ACE2 remained fully active.
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Comment in

Comment on

  • Engineered ACE2 receptor traps potently neutralize SARS-CoV-2.
    Glasgow A, Glasgow J, Limonta D, Solomon P, Lui I, Zhang Y, Nix MA, Rettko NJ, Zha S, Yamin R, Kao K, Rosenberg OS, Ravetch JV, Wiita AP, Leung KK, Lim SA, Zhou XX, Hobman TC, Kortemme T, Wells JA. Glasgow A, et al. Proc Natl Acad Sci U S A. 2020 Nov 10;117(45):28046-28055. doi: 10.1073/pnas.2016093117. Epub 2020 Oct 22. Proc Natl Acad Sci U S A. 2020. PMID: 33093202 Free PMC article.

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