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Comment
. 2021 Apr 13;118(15):e2024450118.
doi: 10.1073/pnas.2024450118.

Reply to Liu et al.: Specific mutations matter in specificity and catalysis in ACE2

Jeff Glasgow  1 , Anum Glasgow  2 , Tanja Kortemme  2 , James A Wells  3
Affiliations
Comment

Reply to Liu et al.: Specific mutations matter in specificity and catalysis in ACE2

Jeff Glasgow et al. Proc Natl Acad Sci U S A. .
No abstract available

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Conflict of interest statement

The authors declare no competing interest.

Figures

Fig. 1.
Fig. 1.
Characterization of Ang II hydrolysis by ACE2 variants using mass spectrometry. (A) CVD208 (wild-type ACE2(740)-Fc) (1 µg/mL) hydrolyzed >90% of Ang II (200 µM) over 60 min at 37 °C. (B) CVD313 (ACE2(740)-Fc (K31F/N33D/H34S/E35Q/H345L) and (C) CVD118 (ACE2(614)-Fc, H34V/N90Q/H374N/H378N) show virtually no detectable hydrolysis of Ang II under the same conditions. Insets in B and C show zoomed-in region containing Ang(1–7), with very little formation from CVD313. (D) Potential substrate-assisted catalysis in ACE2 activity. Based on Guy et al. (9), likely ACE2 residues for oxyanion stabilization include His345 or His505, shown in blue. His6 of Ang II may participate in substrate-assisted catalysis. Three C-terminal residues of Ang II are depicted in red.
See this image and copyright information in PMC

Comment on

References

    1. Glasgow A., et al. ., Engineered ACE2 receptor traps potently neutralize SARS-CoV-2. Proc. Natl. Acad. Sci. U.S.A. 117, 28046–28055. (2020). - PMC - PubMed
    1. Liu P., Xie X., Gao L., Jin J., His345 mutant of angiotensin-converting enzyme 2 (ACE2) remains enzymatically active against angiotensin II. Proc. Natl. Acad. Sci. U.S.A., 10.1073/pnas.2023648118 (2021). - DOI - PMC - PubMed
    1. Liu P., Xie X., Gao L., Jin J., Designed variants of ACE2-Fc that decouple anti-SARS-CoV-2 activities from unwanted cardiovascular effects. Int. J. Biol. Macromol. 165, 1626–1633 (2020). - PMC - PubMed
    1. Monteil V., et al. ., Inhibition of SARS-CoV-2 infections in engineered human tissues using clinical-grade soluble human ACE2. Cell 181, 905–913.e7 (2020). - PMC - PubMed
    1. Lei C., et al. ., Neutralization of SARS-CoV-2 spike pseudotyped virus by recombinant ACE2-Ig. Nat. Commun. 11, 2070 (2020). - PMC - PubMed

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