ArticleThe Journal of biological chemistry2008
Substrate cleavage analysis of furin and related proprotein convertases. A comparative study.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 141 citations in OpenAlex.
- Article
- Variations in "Functional Site" Residues and Classification of Three-Finger Neurotoxins in Snake Venoms.Toxins · 2025Review
- Intracellular trafficking of furin enhances cellular intoxication by recombinant immunotoxins based on Pseudomonas exotoxin A.Biology open · 2025Article
- Targeting the Notch-Furin axis with 2-hydroxyoleic acid: a key mechanism in glioblastoma therapy.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Phytaspase Does Not Require Proteolytic Activity for Its Stress-Induced Internalization.International journal of molecular sciences · 2024Article
- Screening of Small-Molecule Libraries Using SARS-CoV-2-Derived Sequences Identifies Novel Furin Inhibitors.International journal of molecular sciences · 2024Article
- Repurposing clinically available drugs and therapies for pathogenic targets to combat SARS-CoV-2.MedComm · 2023Review
- O-Linked Sialoglycans Modulate the Proteolysis of SARS-CoV-2 Spike and Likely Contribute to the Mutational Trajectory in Variants of Concern.ACS central science · 2023Article
- Roles of host proteases in the entry of SARS-CoV-2.Animal diseases · 2023Review
- Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease.International journal of molecular sciences · 2022Review
- A perspective on the applications of furin inhibitors for the treatment of SARS-CoV-2.Pharmacological reports : PR · 2022Article
- A genetically encoded tool for reconstituting synthetic modulatory neurotransmission and reconnect neural circuits in vivo.Nature communications · 2021Article
- Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza.Life science alliance · 2021Article
- Design and Structure-Activity Relationship of a Potent Furin Inhibitor Derived from Influenza Hemagglutinin.ACS medicinal chemistry letters · 2021Article
- Targeting Crucial Host Factors of SARS-CoV-2.ACS infectious diseases · 2020Review
- Potential Therapeutic Targeting of Coronavirus Spike Glycoprotein Priming.Molecules (Basel, Switzerland) · 2020Article
- Capsids of hepatitis B virus e antigen with authentic C termini are stabilized by electrostatic interactions.FEBS letters · 2020Article
- Development of HiBiT-Tagged Recombinant Infectious Bronchitis Coronavirus for EfficientFrontiers in microbiology · 2020Article
- The Proteolytic Regulation of Virus Cell Entry by Furin and Other Proprotein Convertases.Viruses · 2019Review
- Repeat domain-associated O-glycans govern PMEL fibrillar sheet architecture.Scientific reports · 2019Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
We present the data and the technology, a combination of which allows us to determine the identity of proprotein convertases (PCs) related to the processing of specific protein targets including viral and bacterial pathogens. Our results, which support and extend the data of other laboratories, are required for the design of effective inhibitors of PCs because, in general, an inhibitor design starts with a specific substrate. Seven proteinases of the human PC family cleave the multibasic motifs R-X-(R/K/X)-R downward arrow and, as a result, transform proproteins, including those from pathogens, into biologically active proteins and peptides. The precise cleavage preferences of PCs have not been known in sufficient detail; hence we were unable to determine the relative importance of the individual PCs in infectious diseases, thus making the design of specific inhibitors exceedingly difficult. To determine the cleavage preferences of PCs in more detail, we evaluated the relative efficiency of furin, PC2, PC4, PC5/6, PC7, and PACE4 in cleaving over 100 decapeptide sequences representing the R-X-(R/K/X)-R downward arrow motifs of human, bacterial, and viral proteins. Our computer analysis of the data and the follow-on cleavage analysis of the selected full-length proteins corroborated our initial results thus allowing us to determine the cleavage preferences of the PCs and to suggest which PCs are promising drug targets in infectious diseases. Our results also suggest that pathogens, including anthrax PA83 and the avian influenza A H5N1 (bird flu) hemagglutinin precursor, evolved to be as sensitive to PC proteolysis as the most sensitive normal human proteins.
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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.