7oqq

PARP15 catalytic domain in complex with TIQ-A

spinqualitylabelsall models 7oqq, resolution 2.00Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7oqq 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 2Å Ligands: DMS, G18 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PAR15_HUMAN Transcriptional repressor. Has ADP-ribosyltransferase activity. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Poly(ADP-ribose) polymerase 3D structures

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