1wd8

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[[Image:1wd8.gif|left|200px]]
 
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{{Structure
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==Calcium free form of human peptidylarginine deiminase type4 (PAD4)==
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|PDB= 1wd8 |SIZE=350|CAPTION= <scene name='initialview01'>1wd8</scene>, resolution 2.80&Aring;
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<StructureSection load='1wd8' size='340' side='right'caption='[[1wd8]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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|SITE=
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== Structural highlights ==
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|LIGAND=
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<table><tr><td colspan='2'>[[1wd8]] 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=1WD8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1WD8 FirstGlance]. <br>
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|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Protein-arginine_deiminase Protein-arginine deiminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.3.15 3.5.3.15] </span>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8&#8491;</td></tr>
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|GENE=
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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=1wd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wd8 OCA], [https://pdbe.org/1wd8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1wd8 RCSB], [https://www.ebi.ac.uk/pdbsum/1wd8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1wd8 ProSAT]</span></td></tr>
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|DOMAIN=
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</table>
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|RELATEDENTRY=[[1wd9|1WD9]], [[1wda|1WDA]]
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== Disease ==
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1wd8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1wd8 OCA], [http://www.ebi.ac.uk/pdbsum/1wd8 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1wd8 RCSB]</span>
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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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}}
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== Function ==
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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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'''Calcium free form of human peptidylarginine deiminase type4 (PAD4)'''
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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==Overview==
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<jmolCheckbox>
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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.
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/wd/1wd8_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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==About this Structure==
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<text>to colour the structure by Evolutionary Conservation</text>
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1WD8 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1WD8 OCA].
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</jmolCheckbox>
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</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=1wd8 ConSurf].
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==Reference==
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<div style="clear:both"></div>
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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:[http://www.ncbi.nlm.nih.gov/pubmed/15247907 15247907]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Protein-arginine deiminase]]
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[[Category: Large Structures]]
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[[Category: Single protein]]
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[[Category: Arita K]]
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[[Category: Arita, K.]]
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[[Category: Hashimoto H]]
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[[Category: Hashimoto, H.]]
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[[Category: Nakashima K]]
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[[Category: Nakashima, K.]]
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[[Category: Sato M]]
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[[Category: Sato, M.]]
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[[Category: Shimizu T]]
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[[Category: Shimizu, T.]]
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[[Category: Yamada M]]
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[[Category: Yamada, M.]]
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[[Category: post-translational enzyme]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:34:40 2008''
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Current revision

Calcium free form of human peptidylarginine deiminase type4 (PAD4)

PDB ID 1wd8

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OCA

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