View source for 1wda


==Crystal structure of human peptidylarginine deiminase type4 (PAD4) in complex with benzoyl-L-arginine amide==
<StructureSection load='1wda' size='340' side='right'caption='[[1wda]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1wda]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WDA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WDA FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BAG:N-[(E)-2-AMINO-1-(3-{[AMINO(IMINO)METHYL]AMINO}PROPYL)-2-HYDROXYVINYL]BENZAMIDE'>BAG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=1wda FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wda OCA], [https://pdbe.org/1wda PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wda RCSB], [https://www.ebi.ac.uk/pdbsum/1wda PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wda ProSAT]</span></td></tr>
</table>
== Disease ==
[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> 
== Function ==
[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> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wd/1wda_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1wda ConSurf].
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== Publication Abstract from PubMed ==
Peptidylarginine deiminase 4 (PAD4) is a Ca(2+)-dependent enzyme that catalyzes the conversion of protein arginine residues to citrulline. Its gene is a susceptibility locus for rheumatoid arthritis. Here we present the crystal structure of Ca(2+)-free wild-type PAD4, which shows that the polypeptide chain adopts an elongated fold in which the N-terminal domain forms two immunoglobulin-like subdomains, and the C-terminal domain forms an alpha/beta propeller structure. Five Ca(2+)-binding sites, none of which adopt an EF-hand motif, were identified in the structure of a Ca(2+)-bound inactive mutant with and without bound substrate. These structural data indicate that Ca(2+) binding induces conformational changes that generate the active site cleft. Our findings identify a novel mechanism for enzyme activation by Ca(2+) ions, and are important for understanding the mechanism of protein citrullination and for developing PAD-inhibiting drugs for the treatment of rheumatoid arthritis.

Structural basis for Ca(2+)-induced activation of human PAD4.,Arita K, Hashimoto H, Shimizu T, Nakashima K, Yamada M, Sato M Nat Struct Mol Biol. 2004 Aug;11(8):777-83. Epub 2004 Jul 11. PMID:15247907<ref>PMID:15247907</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 1wda" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Arita K]]
[[Category: Hashimoto H]]
[[Category: Nakashima K]]
[[Category: Sato M]]
[[Category: Shimizu T]]
[[Category: Yamada M]]