View source for 7oth


==PARP15 catalytic domain in complex with OUL219==
<StructureSection load='7oth' size='340' side='right'caption='[[7oth]], [[Resolution|resolution]] 1.70&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7oth]] is a 2 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=7OTH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OTH 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]] 1.7&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=VJN:8-propan-2-yloxy-4~{H}-thieno[2,3-c]isoquinolin-5-one'>VJN</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=7oth FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7oth OCA], [https://pdbe.org/7oth PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7oth RCSB], [https://www.ebi.ac.uk/pdbsum/7oth PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7oth ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/PAR15_HUMAN PAR15_HUMAN] Transcriptional repressor. Has ADP-ribosyltransferase activity.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The scaffold of TIQ-A, a previously known inhibitor of human poly-ADP-ribosyltransferase PARP1, was utilized to develop inhibitors against human mono-ADP-ribosyltransferases through structure-guided design and activity profiling. By supplementing the TIQ-A scaffold with small structural changes, based on a PARP10 inhibitor OUL35, selectivity changed from poly-ADP-ribosyltransferases towards mono-ADP-ribosyltransferases. Binding modes of analogs were experimentally verified by determining complex crystal structures with mono-ADP-ribosyltransferase PARP15 and with poly-ADP-ribosyltransferase TNKS2. The best analogs of the study achieved 10-20-fold selectivity towards mono-ADP-ribosyltransferases PARP10 and PARP15 while maintaining micromolar potencies. The work demonstrates a route to differentiate compound selectivity between mono- and poly-ribosyltransferases of the human ARTD family.

Analogs of TIQ-A as inhibitors of human mono-ADP-ribosylating PARPs.,Maksimainen MM, Murthy S, Sowa ST, Galera-Prat A, Rolina E, Heiskanen JP, Lehtio L Bioorg Med Chem. 2021 Nov 10;52:116511. doi: 10.1016/j.bmc.2021.116511. PMID:34801828<ref>PMID:34801828</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7oth" style="background-color:#fffaf0;"></div>

==See Also==
*[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Lehtio L]]
[[Category: Maksimainen MM]]