ArticleProceedings of the National Academy of Sciences of the United States of America1998
alpha1-Antitrypsin Portland, a bioengineered serpin highly selective for furin: application as an antipathogenic agent.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
118 citing papers in PubMed, 265 citations in OpenAlex.
- U-Net-based reactive center loop-identifier for serpins.Bioinformatics advances · 2026Article
- Kallikrein-8 mediates furin-independent Activin-A precursor processing to stimulate tumor growth in melanoma.Nature communications · 2025Article
- Importance of the (Pro)renin Receptor in Activating the Renin-Angiotensin System During Normotensive and Preeclamptic Pregnancies.Current hypertension reports · 2024Review
- Stepwise release of Activin-A from its inhibitory prodomain is modulated by cysteines and requires furin coexpression to promote melanoma growth.Communications biology · 2024Article
- Alpha-1 antitrypsin inhibits Clostridium botulinum C2 toxin, Corynebacterium diphtheriae diphtheria toxin and B. anthracis fusion toxin.Scientific reports · 2024Article
- Development and Prospects of Furin Inhibitors for Therapeutic Applications.International journal of molecular sciences · 2024Review
- Screening of Small-Molecule Libraries Using SARS-CoV-2-Derived Sequences Identifies Novel Furin Inhibitors.International journal of molecular sciences · 2024Article
- Role of marine natural products in the development of antiviral agents against SARS-CoV-2: potential and prospects.Marine life science & technology · 2024Review
- The Inhibition of Serine Proteases by Serpins Is Augmented by Negatively Charged Heparin: A Concise Review of Some Clinically Relevant Interactions.International journal of molecular sciences · 2024Review
- Association among Lifestyle and Risk Factors with SARS-CoV-2 Infection.Tuberculosis and respiratory diseases · 2023Article
- A perspective on the applications of furin inhibitors for the treatment of SARS-CoV-2.Pharmacological reports : PR · 2022Article
- The Path to Therapeutic Furin Inhibitors: From Yeast Pheromones to SARS-CoV-2.International journal of molecular sciences · 2022Review
- Identification of Kukoamine A, Zeaxanthin, and Clexane as New Furin Inhibitors.International journal of molecular sciences · 2022Article
- Article
- Screening for inhibitory effects of crude drugs on furin-like enzymatic activities.Journal of natural medicines · 2021Article
- FURIN and placental syncytialisation: a cautionary tale.Cell death & disease · 2021Article
- Design and Structure-Activity Relationship of a Potent Furin Inhibitor Derived from Influenza Hemagglutinin.ACS medicinal chemistry letters · 2021Article
- Mechanisms in Which Smoking Increases the Risk of COVID-19 Infection: A Narrative Review.Iranian journal of public health · 2021Review
- Translating bioactive peptides for COVID-19 therapy.European journal of pharmacology · 2021Review
- Does Covera-19 know 'when to hold 'em or 'when to fold 'em? A translational thought experiment.Translational medicine communications · 2021Review
58 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The important role of furin in the proteolytic activation of many pathogenic molecules has made this endoprotease a target for the development of potent and selective antiproteolytic agents. Here, we demonstrate the utility of the protein-based inhibitor alpha1-antitrypsin Portland (alpha1-PDX) as an antipathogenic agent that can be used prophylactically to block furin-dependent cell killing by Pseudomonas exotoxin A. Biochemical analysis of the specificity of a bacterially expressed His- and FLAG-tagged alpha1-PDX (alpha1-PDX/hf) revealed the selectivity of the alpha1-PDX/hf reactive site loop for furin (Ki, 600 pM) but not for other proprotein convertase family members or other unrelated endoproteases. Kinetic studies show that alpha1-PDX/hf inhibits furin by a slow tight-binding mechanism characteristic of serpin molecules and functions as a suicide substrate inhibitor. Once bound to furin's active site, alpha1-PDX/hf partitions with equal probability to undergo proteolysis by furin at the C-terminal side of the reactive center -Arg355-Ile-Pro-Arg358- downward arrow or to form a kinetically trapped SDS-stable complex with the enzyme. This partitioning between the complex-forming and proteolytic pathways contributes to the ability of alpha1-PDX/hf to differentially inhibit members of the proprotein convertase family. Finally, we propose a structural model of the alpha1-PDX-reactive site loop that explains the high degree of enzyme selectivity of this serpin and which can be used to generate small molecule furin inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
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.