7r4a: Difference between revisions

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7r4a]] 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=7R4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4A FirstGlance]. <br>
<table><tr><td colspan='2'>[[7r4a]] 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=7R4A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7R4A FirstGlance]. <br>
</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=I1B:6,8-dimethyl-[1,2,4]triazolo[3,4-b][1,3]benzothiazole'>I1B</scene></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.9&#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=I1B:6,8-dimethyl-[1,2,4]triazolo[3,4-b][1,3]benzothiazole'>I1B</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=7r4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4a OCA], [https://pdbe.org/7r4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4a RCSB], [https://www.ebi.ac.uk/pdbsum/7r4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4a ProSAT]</span></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=7r4a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r4a OCA], [https://pdbe.org/7r4a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r4a RCSB], [https://www.ebi.ac.uk/pdbsum/7r4a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r4a ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[https://www.uniprot.org/uniprot/PAR15_HUMAN PAR15_HUMAN] Transcriptional repressor. Has ADP-ribosyltransferase activity.
[https://www.uniprot.org/uniprot/PAR15_HUMAN PAR15_HUMAN] Transcriptional repressor. Has ADP-ribosyltransferase activity.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We report [1,2,4]triazolo[3,4-b]benzothiazole (TBT) as a new inhibitor scaffold, which competes with nicotinamide in the binding pocket of human poly- and mono-ADP-ribosylating enzymes. The binding mode was studied through analogues and cocrystal structures with TNKS2, PARP2, PARP14, and PARP15. Based on the substitution pattern, we were able to identify 3-amino derivatives 21 (OUL243) and 27 (OUL232) as inhibitors of mono-ARTs PARP7, PARP10, PARP11, PARP12, PARP14, and PARP15 at nM potencies, with 27 being the most potent PARP10 inhibitor described to date (IC(50) of 7.8 nM) and the first PARP12 inhibitor ever reported. On the contrary, hydroxy derivative 16 (OUL245) inhibits poly-ARTs with a selectivity toward PARP2. The scaffold does not possess inherent cell toxicity, and the inhibitors can enter cells and engage with the target protein. This, together with favorable ADME properties, demonstrates the potential of TBT scaffold for future drug development efforts toward selective inhibitors against specific enzymes.


[1,2,4]Triazolo[3,4-b]benzothiazole Scaffold as Versatile Nicotinamide Mimic Allowing Nanomolar Inhibition of Different PARP Enzymes.,Murthy S, Nizi MG, Maksimainen MM, Massari S, Alaviuhkola J, Lippok BE, Vagaggini C, Sowa ST, Galera-Prat A, Ashok Y, Venkannagari H, Prunskaite-Hyyrylainen R, Dreassi E, Luscher B, Korn P, Tabarrini O, Lehtio L J Med Chem. 2023 Jan 4. doi: 10.1021/acs.jmedchem.2c01460. PMID:36598465<ref>PMID:36598465</ref>
==See Also==
 
*[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]]
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7r4a" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Latest revision as of 11:00, 7 February 2024

PARP15 catalytic domain in complex with OUL188PARP15 catalytic domain in complex with OUL188

Structural highlights

7r4a is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.9Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PAR15_HUMAN Transcriptional repressor. Has ADP-ribosyltransferase activity.

See Also

7r4a, resolution 1.90Å

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