Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase*

By Chad Vickers, P. Hales, V. Kaushik, L. Dick, James M. Gavin, Jin Tang, Kevin Godbout, T. Parsons, E. Baronas, F. Hsieh and 4 more. Journal of Biological Chemistry, 2002

1,396 citations recorded by the source corpus.

Human angiotensin-converting enzyme-related carboxypeptidase (ACE2) is a zinc metalloprotease whose closest homolog is angiotensin I-converting enzyme. To begin to elucidate the physiological role of ACE2, ACE2 was purified, and its catalytic activity was characterized. ACE2 proteolytic activity has a pH optimum of 6.5 and is enhanced by monovalent anions, which is consistent with the activity of ACE. ACE2 activity is increased ∼10-fold by Cl− and F− but is unaffected by Br−. ACE2 was screened for hydrolytic activity against a panel of 126 biological peptides, using liquid chromatography-mass spectrometry detection. Eleven of the peptides were hydrolyzed by ACE2, and in each case, the proteolytic activity resulted in removal of the C-terminal residue only. ACE2 hydrolyzes three of the peptides with high catalytic efficiency: angiotensin II (1-8) (k cat/K m = 1.9 × 106 m −1 s−1), apelin-13 (k cat/K m = 2.1 × 106 m −1s−1), and dynorphin A 1–13 (k cat/K m = 3.1 × 106 m −1 s−1). The ACE2 catalytic efficiency is 400-fold higher with angiotensin II (1-8) as a substrate than with angiotensin I (1-10). ACE2 also efficiently hydrolyzes des-Arg9-bradykinin (k cat/K m = 1.3 × 105 m −1 s−1), but it does not hydrolyze bradykinin. An alignment of the ACE2 peptide substrates reveals a consensus sequence of: Pro-X (1–3 residues)-Pro-Hydrophobic, where hydrolysis occurs between proline and the hydrophobic amino acid.

Subfields: Cardiology and Cardiovascular Medicine, Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/194d82db4ba5da9e457bd8fda6ce191b956bdb8d

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In Cardiology and Cardiovascular Medicine

1. M. Grant
2. J. Zhong
3. Vaibhav B. Patel
4. G. Oudit

In Molecular Biology

1. M. Grant
2. J. Zhong
3. Vaibhav B. Patel
4. G. Oudit
5. P. Masters

Citations in the corpus

• Risk factors of critical & mortal COVID-19 cases: A systematic literature review and meta-analysis (2020, background): “The main role of ACE2 is to incise Ang II to generate Ang 1-7, which mediates the protective effects of vasodilation, anti-inflammatory and anti-proliferation, to antagonize Ang II-induced vascular smooth muscle contraction, cell proliferation, fibrosis promotion and vascular inflammation [21] [22] ”
• Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus (2003, background): “Candidate substrates, some of which regulate vasopermeability, have been identifie”
• Role of the ACE2/Angiotensin 1–7 axis of the Renin-Angiotensin System in Heart Failure (2016, methodology): “lytic efficiency is 400-fold higher with Ang II as a substrate than with Ang I.(38,42) To further unravel the biological role and”
• The pivotal link between ACE2 deficiency and SARS-CoV-2 infection (2020, neutral): “[6] ACE2 shows a 40% structural identity to ACE, [4] although ACE-inhibitors do not block ACE2 because of the different conformational structure of the catalytic site.”