8sml

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Current revision (05:26, 12 June 2024) (edit) (undo)
 
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8sml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sml OCA], [https://pdbe.org/8sml PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sml RCSB], [https://www.ebi.ac.uk/pdbsum/8sml PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sml ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8sml FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8sml OCA], [https://pdbe.org/8sml PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8sml RCSB], [https://www.ebi.ac.uk/pdbsum/8sml PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8sml ProSAT]</span></td></tr>
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== Disease ==
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<div style="background-color:#fffaf0;">
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[https://www.uniprot.org/uniprot/PADI4_HUMAN PADI4_HUMAN] Genetic variations in PADI4 are a cause of susceptibility to rheumatoid arthritis (RA) [MIM:[https://omim.org/entry/180300 180300]. It is a systemic inflammatory disease with autoimmune features and a complex genetic component. It primarily affects the joints and is characterized by inflammatory changes in the synovial membranes and articular structures, widespread fibrinoid degeneration of the collagen fibers in mesenchymal tissues, and by atrophy and rarefaction of bony structures. Note=Could have an important role in the pathogenesis of rheumatoid arthritis by increasing citrullination of proteins in rheumatoid arthritis synovial tissues, leading, in a cytokine-rich milieu, to a break in tolerance to citrullinated peptides processed and presented in the appropriate HLA context.<ref>PMID:12833157</ref>
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== Publication Abstract from PubMed ==
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== Function ==
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Unlocking the potential of protein arginine deiminase 4 (PAD4) as a drug target for rheumatoid arthritis requires a deeper understanding of its regulation. In this study, we use unbiased antibody selections to identify functional antibodies capable of either activating or inhibiting PAD4 activity. Through cryogenic-electron microscopy, we characterized the structures of these antibodies in complex with PAD4 and revealed insights into their mechanisms of action. Rather than steric occlusion of the substrate-binding catalytic pocket, the antibodies modulate PAD4 activity through interactions with allosteric binding sites adjacent to the catalytic pocket. These binding events lead to either alteration of the active site conformation or the enzyme oligomeric state, resulting in modulation of PAD4 activity. Our study uses antibody engineering to reveal new mechanisms for enzyme regulation and highlights the potential of using PAD4 agonist and antagonist antibodies for studying PAD4-dependency in disease models and future therapeutic development.
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[https://www.uniprot.org/uniprot/PADI4_HUMAN PADI4_HUMAN] Catalyzes the citrullination/deimination of arginine residues of proteins. Citrullinates histone H3 at 'Arg-8' and/or 'Arg-17' and histone H4 at 'Arg-3', which prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription. Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1.<ref>PMID:15339660</ref> <ref>PMID:15345777</ref>
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Antibody discovery identifies regulatory mechanisms of protein arginine deiminase 4.,Zhou X, Kong S, Maker A, Remesh SG, Leung KK, Verba KA, Wells JA Nat Chem Biol. 2024 Jun;20(6):742-750. doi: 10.1038/s41589-023-01535-8. Epub 2024 , Feb 2. PMID:38308046<ref>PMID:38308046</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 8sml" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Current revision

hPAD4 bound to inhibitory Fab hI365

PDB ID 8sml

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