5o2d: Difference between revisions
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==PARP14 Macrodomain 2 with inhibitor== | ==PARP14 Macrodomain 2 with inhibitor== | ||
<StructureSection load='5o2d' size='340' side='right' caption='[[5o2d]], [[Resolution|resolution]] 1.60Å' scene=''> | <StructureSection load='5o2d' size='340' side='right'caption='[[5o2d]], [[Resolution|resolution]] 1.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5o2d]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5o2d]] 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=5O2D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O2D FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.6Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9HH:~{N}-[2-(9~{H}-carbazol-1-yl)phenyl]methanesulfonamide'>9HH</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=5o2d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o2d OCA], [https://pdbe.org/5o2d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o2d RCSB], [https://www.ebi.ac.uk/pdbsum/5o2d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o2d ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/PAR14_HUMAN PAR14_HUMAN] Enhances STAT6-dependent transcription (By similarity). Has ADP-ribosyltransferase activity. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 5o2d" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 5o2d" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Arrowsmith | [[Category: Large Structures]] | ||
[[Category: Bountra | [[Category: Arrowsmith C]] | ||
[[Category: Bracher | [[Category: Bountra C]] | ||
[[Category: Edwards | [[Category: Bracher F]] | ||
[[Category: Elkins | [[Category: Edwards AM]] | ||
[[Category: Knapp | [[Category: Elkins JM]] | ||
[[Category: Krojer | [[Category: Knapp S]] | ||
[[Category: Riedels | [[Category: Krojer T]] | ||
[[Category: Riedels K]] | |||
[[Category: Schuller | [[Category: Schuller M]] | ||
[[Category: Sieg | [[Category: Sieg C]] | ||
[[Category: Uth | [[Category: Uth K]] | ||
[[Category: Wang | [[Category: Wang J]] | ||
Latest revision as of 22:04, 29 November 2023
PARP14 Macrodomain 2 with inhibitorPARP14 Macrodomain 2 with inhibitor
Structural highlights
FunctionPAR14_HUMAN Enhances STAT6-dependent transcription (By similarity). Has ADP-ribosyltransferase activity. Publication Abstract from PubMedMacrodomains are conserved protein interaction modules that can be found in all domains of life including in certain viruses. Macrodomains mediate recognition of sequence motifs harboring adenosine diphosphate ribose (ADPR) modifications, thereby regulating a variety of cellular processes. Due to their role in cancer or viral pathogenesis, macrodomains have emerged as potential therapeutic targets, but the unavailability of small molecule inhibitors has hampered target validation studies so far. Here, we describe an efficient screening strategy for identification of small molecule inhibitors that displace ADPR from macrodomains. We report the discovery and characterization of a macrodomain inhibitor, GeA-69, selectively targeting macrodomain 2 (MD2) of PARP14 with low micromolar affinity. Co-crystallization of a GeA-69 analogue with PARP14 MD2 revealed an allosteric binding mechanism explaining its selectivity over other human macrodomains. We show that GeA-69 engages PARP14 MD2 in intact cells and prevents its localization to sites of DNA damage. Discovery of a Selective Allosteric Inhibitor Targeting Macrodomain 2 of Polyadenosine-Diphosphate-Ribose Polymerase 14.,Schuller M, Riedel K, Gibbs-Seymour I, Uth K, Sieg C, Gehring AP, Ahel I, Bracher F, Kessler BM, Elkins JM, Knapp S ACS Chem Biol. 2017 Oct 19. doi: 10.1021/acschembio.7b00445. PMID:28991428[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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