View source for 9b97


==Crystal structure of the human PAD2 protein bound to small molecule==
<StructureSection load='9b97' size='340' side='right'caption='[[9b97]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9b97]] 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=9B97 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9B97 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]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1AJB:5-[3-[[(2~{R})-3-cyclohexyl-1-(methylamino)-1-oxidanylidene-propan-2-yl]carbamoyl]-5-[[4-(4-phenylbutyl)piperazin-1-yl]methyl]phenyl]-~{N},~{N}-diethyl-2-fluoranyl-benzamide'>A1AJB</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=MPD:(4S)-2-METHYL-2,4-PENTANEDIOL'>MPD</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=9b97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9b97 OCA], [https://pdbe.org/9b97 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9b97 RCSB], [https://www.ebi.ac.uk/pdbsum/9b97 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9b97 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PADI2_HUMAN PADI2_HUMAN] Catalyzes the deimination of arginine residues of proteins.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Peptidyl arginine deiminases (PADs) are important enzymes in many diseases, especially those involving inflammation and autoimmunity. Despite many years of effort, developing isoform-specific inhibitors has been a challenge. We describe herein the discovery of a potent, noncovalent PAD2 inhibitor, with selectivity over PAD3 and PAD4, from a DNA-encoded library. The biochemical and biophysical characterization of this inhibitor and two noninhibitory binders indicated a novel, Ca(2+) competitive mechanism of inhibition. This was confirmed via X-ray crystallographic analysis. Finally, we demonstrate that this inhibitor selectively inhibits PAD2 in a cellular context.

Discovery, Characterization, and Structure of a Cell Active PAD2 Inhibitor Acting through a Novel Allosteric Mechanism.,Byrnes LJ, Choi WY, Balbo P, Banker ME, Chang J, Chen S, Cheng X, Cong Y, Culp J, Di H, Griffor M, Hall J, Meng X, Morgan B, Mousseau JJ, Nicki J, O'Connell T, Ramsey S, Shaginian A, Shanker S, Trujillo J, Wan J, Vincent F, Wright SW, Vajdos F ACS Chem Biol. 2024 Sep 24. doi: 10.1021/acschembio.4c00397. PMID:39316753<ref>PMID:39316753</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9b97" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Byrnes LJ]]
[[Category: Vajdos F]]