5lxp
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==Human PARP14 (ARTD8), catalytic fragment in complex with inhibitor H5== | |
| + | <StructureSection load='5lxp' size='340' side='right' caption='[[5lxp]], [[Resolution|resolution]] 2.07Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5lxp]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LXP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LXP FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7AG:~{N}-(3-AMINOCARBONYLPHENYL)-~{N}-[[1-[(2~{R})-2-PHENYLPROPYL]-1,2,3-TRIAZOL-4-YL]METHYL]PENTANEDIAMIDE'>7AG</scene></td></tr> | ||
| + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5lxp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lxp OCA], [http://pdbe.org/5lxp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lxp RCSB], [http://www.ebi.ac.uk/pdbsum/5lxp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lxp ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/PAR14_HUMAN PAR14_HUMAN]] Enhances STAT6-dependent transcription (By similarity). Has ADP-ribosyltransferase activity. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Poly(ADP-ribose) polymerases (PARPs) are key enzymes in a variety of cellular processes. Most small-molecule PARP inhibitors developed to date have been against PARP1, and suffer from poor selectivity. PARP14 has recently emerged as a potential therapeutic target, but its inhibitor development has trailed behind. Herein, we describe a small molecule microarray-based strategy for high-throughput synthesis, screening of >1000 potential bidentate inhibitors of PARPs, and the successful discovery of a potent PARP14 inhibitor H10 with >20-fold selectivity over PARP1. Co-crystallization of the PARP14/H10 complex indicated H10 bound to both the nicotinamide and the adenine subsites. Further structure-activity relationship studies identified important binding elements in the adenine subsite. In tumor cells, H10 was able to chemically knockdown endogenous PARP14 activities. | ||
| - | + | Small Molecule Microarray Based Discovery of PARP14 Inhibitors.,Peng B, Thorsell AG, Karlberg T, Schuler H, Yao SQ Angew Chem Int Ed Engl. 2016 Dec 5. doi: 10.1002/anie.201609655. PMID:27918638<ref>PMID:27918638</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 5lxp" style="background-color:#fffaf0;"></div> | |
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
[[Category: Karlberg, T]] | [[Category: Karlberg, T]] | ||
[[Category: Schuler, H]] | [[Category: Schuler, H]] | ||
| + | [[Category: Thorsell, A G]] | ||
| + | [[Category: Adp-ribosylation]] | ||
| + | [[Category: Inhibitor complex]] | ||
| + | [[Category: Transferase]] | ||
| + | [[Category: Transferase domain]] | ||
Revision as of 21:34, 22 December 2016
Human PARP14 (ARTD8), catalytic fragment in complex with inhibitor H5
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