ArticleACS chemical biology2015
Protein arginine deiminase 2 binds calcium in an ordered fashion: implications for inhibitor design.
Article in ACS chemical biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 123 citations in OpenAlex.
- Decoding isozyme-specific substrate recognition in protein arginine deiminases by in vitro lysate-based citrullination mapping.Nature communications · 2026Article
- Citrullination and Deamidation in Type 1 Diabetes: Linking Beta Cell Stress to Neoantigen-Driven Autoimmunity.Immunological reviews · 2026Review
- The TG2/LRP1 Pathway for T Cell Activation by Post-Translationally Modified Antigens.Immunological reviews · 2026Review
- Article
- Differential histone tail citrullination by PAD Enzymes observed via NMR spectroscopy.bioRxiv : the preprint server for biology · 2026Article
- Beyond PAD Inhibition: Emerging Avenues and Natural Products for Targeting Citrullination in Immune Diseases.Biomedicines · 2026Review
- Peptidylarginine deiminase 4-mediated citrullination in human disease: molecular mechanisms and therapeutic targeting.Frontiers in pharmacology · 2026Review
- Inhibition of <italic>Pseudomonas aeruginosa</italic> Biofilm Formation by Peptidyl-Arginine Deiminases 2 and 4.Journal of innate immunity · 2026Article
- Hydrogen sulphide modifies the therapeutic potential of bone marrow mesenchymal stem cells in an adjuvant-induced polyarthritis rat model through the mitigation of angiogenesis, ectopic lymphoid tissue formation, and osteoclastogenesis.Inflammopharmacology · 2026Article
- Probing tau citrullination in Alzheimer's disease brains and mouse models of tauopathy.Acta neuropathologica · 2025Article
- PAD2 disturbs cardiomyocyte calcium homeostasis by citrullinating SERCA2a protein in hemorrhagic shock induced arrhythmia.The journal of trauma and acute care surgery · 2025Article
- Inhibiting peptidylarginine deiminases (PAD1-4) by targeting a CaNature communications · 2025Article
- Optogenetics with Atomic Precision─A Comprehensive Review of Optical Control of Protein Function through Genetic Code Expansion.Chemical reviews · 2025Review
- Structural insight into the function of human peptidyl arginine deiminase 6.Computational and structural biotechnology journal · 2024Article
- Identification of novel PAD2 inhibitors using pharmacophore-based virtual screening, molecular docking, and MD simulation studies.Scientific reports · 2024Article
- A cyclic peptide toolkit reveals mechanistic principles of peptidylarginine deiminase IV regulation.Nature communications · 2024Article
- Antibody discovery identifies regulatory mechanisms of protein arginine deiminase 4.Nature chemical biology · 2024Article
- Modes of PADing.Nature chemical biology · 2024Article
- Crystal structure of human peptidylarginine deiminase type VI (PAD6) provides insights into its inactivity.IUCrJ · 2024Article
- Evolutionary analysis reveals the role of a non-catalytic domain of peptidyl arginine deiminase 2 in transcriptional regulation.iScience · 2024Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Protein arginine deiminases (PADs) are calcium-dependent histone-modifying enzymes whose activity is dysregulated in inflammatory diseases and cancer. PAD2 functions as an Estrogen Receptor (ER) coactivator in breast cancer cells via the citrullination of histone tail arginine residues at ER binding sites. Although an attractive therapeutic target, the mechanisms that regulate PAD2 activity are largely unknown, especially the detailed role of how calcium facilitates enzyme activation. To gain insights into these regulatory processes, we determined the first structures of PAD2 (27 in total), and through calcium-titrations by X-ray crystallography, determined the order of binding and affinity for the six calcium ions that bind and activate this enzyme. These structures also identified several PAD2 regulatory elements, including a calcium switch that controls proper positioning of the catalytic cysteine residue, and a novel active site shielding mechanism. Additional biochemical and mass-spectrometry-based hydrogen/deuterium exchange studies support these structural findings. The identification of multiple intermediate calcium-bound structures along the PAD2 activation pathway provides critical insights that will aid the development of allosteric inhibitors targeting the PADs.
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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.