ArticleThe Biochemical journal2005
The N domain of somatic angiotensin-converting enzyme negatively regulates ectodomain shedding and catalytic activity.
Article in The Biochemical journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 45 citations in OpenAlex.
- Advances in the structural basis for angiotensin-1 converting enzyme (ACE) inhibitors.Bioscience reports · 2024Review
- Re-evaluating serum angiotensin-converting enzyme in sarcoidosis.Frontiers in immunology · 2023Review
- Interacting cogs in the machinery of the renin angiotensin system.Biophysical reviews · 2019Review
- Conformational Fingerprinting Using Monoclonal Antibodies (on the Example of Angiotensin I-Converting Enzyme-ACE).Molecular biology · 2017Article
- QM/MM investigation of the catalytic mechanism of angiotensin-converting enzyme.Journal of molecular modeling · 2016Article
- Kinetic and structural characterization of amyloid-β peptide hydrolysis by human angiotensin-1-converting enzyme.The FEBS journal · 2016Article
- Structural basis of Ac-SDKP hydrolysis by Angiotensin-I converting enzyme.Scientific reports · 2015Article
- Rediscovering ACE: novel insights into the many roles of the angiotensin-converting enzyme.Journal of molecular medicine (Berlin, Germany) · 2013Review
- A modern understanding of the traditional and nontraditional biological functions of angiotensin-converting enzyme.Pharmacological reviews · 2013Review
- Targeted catalytic inactivation of angiotensin converting enzyme by lisinopril-coupled transition-metal chelates.Journal of the American Chemical Society · 2012Article
- A small region in the angiotensin-converting enzyme distal ectodomain is required for cleavage-secretion of the protein at the plasma membrane.Biochemistry · 2008Article
- The angiotensin-converting enzyme (ACE) gene family of Anopheles gambiae.BMC genomics · 2005Article
- Kinetic probes for inter-domain co-operation in human somatic angiotensin-converting enzyme.The Biochemical journal · 2005Article
- Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2).The Journal of biological chemistry · 2005Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
sACE (somatic angiotensin-converting enzyme) consists of two homologous, N and C domains, whereas the testis isoenzyme [tACE (testis ACE)] consists of a single C domain. Both isoenzymes are shed from the cell surface by a sheddase activity, although sACE is shed much less efficiently than tACE. We hypothesize that the N domain of sACE plays a regulatory role, by occluding a recognition motif on the C domain required for ectodomain shedding and by influencing the catalytic efficiency. To test this, we constructed two mutants: CNdom-ACE and CCdom-ACE. CNdom-ACE was shed less efficiently than sACE, whereas CCdom-ACE was shed as efficiently as tACE. Notably, cleavage occurred both within the stalk and the interdomain bridge in both mutants, suggesting that a sheddase recognition motif resides within the C domain and is capable of directly cleaving at both positions. Analysis of the catalytic properties of the mutants and comparison with sACE and tACE revealed that the k(cat) for sACE and CNdom-ACE was less than or equal to the sum of the kcat values for tACE and the N-domain, suggesting negative co-operativity, whereas the kcat value for the CCdom-ACE suggested positive co-operativity between the two domains. Taken together, the results provide support for (i) the existence of a sheddase recognition motif in the C domain and (ii) molecular flexibility of the N and C domains in sACE, resulting in occlusion of the C-domain recognition motif by the N domain as well as close contact of the two domains during hydrolysis of peptide substrates.
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