ArticlePloS one2011
An angiotensin I-converting enzyme mutation (Y465D) causes a dramatic increase in blood ACE via accelerated ACE shedding.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 51 citations in OpenAlex.
- Alzheimer's disease-linked ACE variants increase ACE1 catalytic activity and production of angiotensin II.The Journal of biological chemistry · 2026Article
- Dimerization and dynamics of human angiotensin-I converting enzyme revealed by cryo-EM and MD simulations.eLife · 2025Article
- Effects of Angiotensin-I-Converting Enzyme (ACE) Mutations Associated with Alzheimer's Disease on Blood ACE Phenotype.Biomedicines · 2024Article
- Advances in the structural basis for angiotensin-1 converting enzyme (ACE) inhibitors.Bioscience reports · 2024Review
- ACE Phenotyping in Human Blood and Tissues: Revelation of ACE Outliers and Sex Differences in ACE Sialylation.Biomedicines · 2024Article
- Urinary ACE Phenotyping as a Research and Diagnostic Tool: Identification of Sex-Dependent ACE Immunoreactivity.Biomedicines · 2023Article
- Blood ACE Phenotyping for Personalized Medicine: Revelation of Patients with Conformationally Altered ACE.Biomedicines · 2023Article
- Natural products and drug discovery.National science review · 2022Review
- Predictive potential of ACE phenotyping in extrapulmonary sarcoidosis.Respiratory research · 2022Article
- Cryo-EM reveals mechanisms of angiotensin I-converting enzyme allostery and dimerization.The EMBO journal · 2022Article
- Epitope mapping of novel monoclonal antibodies to human angiotensin I-converting enzyme.Protein science : a publication of the Protein Society · 2021Article
- The renin-angiotensin system in COVID-19: Why ACE2 targeting by coronaviruses produces higher mortality in elderly hypertensive patients?BioEssays : news and reviews in molecular, cellular and developmental biology · 2021Review
- Interacting cogs in the machinery of the renin angiotensin system.Biophysical reviews · 2019Review
- Tissue ACE phenotyping in lung cancer.PloS one · 2019Article
- Article
- Conformational Fingerprinting Using Monoclonal Antibodies (on the Example of Angiotensin I-Converting Enzyme-ACE).Molecular biology · 2017Article
- Markers and Biomarkers of Endothelium: When Something Is Rotten in the State.Oxidative medicine and cellular longevity · 2017Review
- Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding.Scientific reports · 2016Article
- Local Augmented Angiotensinogen Secreted from Apoptotic Vascular Endothelial Cells Is a Vital Mediator of Vascular Remodelling.PloS one · 2015Article
- Absence of cell surface expression of human ACE leads to perinatal death.Human molecular genetics · 2014Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundAngiotensin I-converting enzyme (ACE) metabolizes a range of peptidic substrates and plays a key role in blood pressure regulation and vascular remodeling. Thus, elevated ACE levels may be associated with an increased risk for different cardiovascular or respiratory diseases. Previously, a striking familial elevation in blood ACE was explained by mutations in the ACE juxtamembrane region that enhanced the cleavage-secretion process. Recently, we found a family whose affected members had a 6-fold increase in blood ACE and a Tyr465Asp (Y465D) substitution, distal to the stalk region, in the N domain of ACE. METHODOLOGY/PRINCIPAL
findingsHEK and CHO cells expressing mutant (Tyr465Asp) ACE demonstrate a 3- and 8-fold increase, respectively, in the rate of ACE shedding compared to wild-type ACE. Conformational fingerprinting of mutant ACE demonstrated dramatic changes in ACE conformation in several different epitopes of ACE. Cell ELISA carried out on CHO-ACE cells also demonstrated significant changes in local ACE conformation, particularly proximal to the stalk region. However, the cleavage site of the mutant ACE--between Arg1203 and Ser1204--was the same as that of WT ACE. The Y465D substitution is localized in the interface of the N-domain dimer (from the crystal structure) and abolishes a hydrogen bond between Tyr465 in one monomer and Asp462 in another. CONCLUSIONS/SIGNIFICANCE: The Y465D substitution results in dramatic increase in the rate of ACE shedding and is associated with significant local conformational changes in ACE. These changes could result in increased ACE dimerization and accessibility of the stalk region or the entire sACE, thus increasing the rate of cleavage by the putative ACE secretase (sheddase).
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.