ArticleNature communications2025
Inhibiting peptidylarginine deiminases (PAD1-4) by targeting a Ca
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- PAD4-DB: A Curated Structure-Activity Resource Reveals Hub-Organized Activity Cliffs and Scaffold-Dependent SAR Ruggedness in PAD4 Inhibitors.International journal of molecular sciences · 2026Article
- Decoding isozyme-specific substrate recognition in protein arginine deiminases by in vitro lysate-based citrullination mapping.Nature communications · 2026Article
- Mapping the Substrate Specificity Landscape of PAD2 and PAD4 Enzymes.Chembiochem : a European journal of chemical biology · 2026Article
- Insulin preservatives trigger neutrophil extracellular trap formation through SYNE1-mediated nuclear disassembly.bioRxiv : the preprint server for biology · 2026Article
- Targeting Peptidylarginine Deiminases in Neurons and Astrocytes in Central Nervous System Injury-Effects of Pan-PAD Inhibitor Cl-Amidine in an Oxygen-Glucose Deprivation Model of Ischaemia (OGD/R) and LPS Stimulation In Vitro.International journal of molecular sciences · 2026Article
- Beyond PAD Inhibition: Emerging Avenues and Natural Products for Targeting Citrullination in Immune Diseases.Biomedicines · 2026Review
- Role of peptidylarginine deiminase 2 in a murine model of traumatic brain injury.The journal of trauma and acute care surgery · 2026Article
- Peptidylarginine deiminase 4-mediated citrullination in human disease: molecular mechanisms and therapeutic targeting.Frontiers in pharmacology · 2026Review
- Mapping benefit, risk, and opportunity in PAD4 inhibition.Frontiers in immunology · 2026Review
- Roles of peptidylarginine deiminase (PAD) and protein citrullination in viral infections.Frontiers in microbiology · 2026Review
- Peptidylarginine Deiminases: An Overview of Recent Advances in Citrullination Research.International journal of molecular sciences · 2025Review
- Ketone body β-hydroxybutyrate-mediated histone β-hydroxybutyrylation upregulates lipolysis and attenuates metabolic syndrome.American journal of physiology. Cell physiology · 2025Article
- Peptidylarginine Deiminase (PAD) Inhibitor Optimization through Displacement of a Trapped Water Molecule.ACS medicinal chemistry letters · 2025Article
Corrections and comments
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Authors and funding
26 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Peptidylarginine deiminases (PAD1-4) are calcium dependent enzymes responsible for protein citrullination, a post-translational modification converting arginine residues to citrulline. Elevated levels of citrullinated proteins have been associated with rheumatoid arthritis, neurodegenerative diseases, and cancers. Though highly selective PAD4 inhibitors have been described, inhibitors to the broader family currently are limited to covalent substrate analogs. Herein, we describe an allosteric binding pocket common to PAD1-4 suitable for the identification of potent, non-covalent enzyme inhibitors. A ligand-based virtual screen is utilized to identify a PAD4 inhibitor for which surface plasmon resonance confirms target binding but non-competitively with a known PAD4 ligand. We further show through co-crystal structure analysis that the ligand binds PAD4 at an allosteric pocket resulting in stabilization of a catalytically inactive, calcium-deficient enzyme conformation. A ligand designed based on this site potently inhibits all four PAD isozymes and prevents protein citrullination in neutrophils with a broader protein repertoire than observed with a PAD4-selective inhibitor.
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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.