7osp: Difference between revisions
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==PARP15 catalytic domain in complex with OUL113== | |||
<StructureSection load='7osp' size='340' side='right'caption='[[7osp]], [[Resolution|resolution]] 1.44Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7osp]] 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=7OSP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7OSP 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]] 1.44Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0Q6:4-[(3-bromophenyl)methoxy]benzamide'>0Q6</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=7osp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7osp OCA], [https://pdbe.org/7osp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7osp RCSB], [https://www.ebi.ac.uk/pdbsum/7osp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7osp 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7osp" style="background-color:#fffaf0;"></div> | ||
[[Category: Lehtio | |||
==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]] | |||
Latest revision as of 15:55, 1 February 2024
PARP15 catalytic domain in complex with OUL113PARP15 catalytic domain in complex with OUL113
Structural highlights
FunctionPAR15_HUMAN Transcriptional repressor. Has ADP-ribosyltransferase activity. Publication Abstract from PubMedThe 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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