5lx6: Difference between revisions

Revision as of 10:53, 12 August 2020

Human PARP10 (ARTD10), catalytic fragment in complex with PARP inhibitor Veliparib

Structural highlights

5lx6 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	78P
Gene:	PARP10 (HUMAN)
Activity:	NAD(+) ADP-ribosyltransferase, with EC number 2.4.2.30
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PAR10_HUMAN] May play a role in cell proliferation. May be required for the maintenance of cell cycle progression.^[1] ^[2]

Publication Abstract from PubMed

Selective inhibitors could help unveil the mechanisms by which inhibition of poly(ADP-ribose) polymerases (PARPs) elicits clinical benefits in cancer therapy. We profiled 10 clinical PARP inhibitors and commonly used research tools for their inhibition of multiple PARP enzymes. We also determined crystal structures of these compounds bound to PARP1 or PARP2. Veliparib and niraparib are selective inhibitors of PARP1 and PARP2; olaparib, rucaparib, and talazoparib are more potent inhibitors of PARP1 but are less selective. PJ34 and UPF1069 are broad PARP inhibitors; PJ34 inserts a flexible moiety into hydrophobic subpockets in various ADP-ribosyltransferases. XAV939 is a promiscuous tankyrase inhibitor and a potent inhibitor of PARP1 in vitro and in cells, whereas IWR1 and AZ-6102 are tankyrase selective. Our biochemical and structural analysis of PARP inhibitor potencies establishes a molecular basis for either selectivity or promiscuity and provides a benchmark for experimental design in assessment of PARP inhibitor effects.

Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors.,Thorsell AG, Ekblad T, Karlberg T, Low M, Pinto AF, Tresaugues L, Moche M, Cohen MS, Schuler H J Med Chem. 2016 Dec 21. PMID:28001384^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yu M, Schreek S, Cerni C, Schamberger C, Lesniewicz K, Poreba E, Vervoorts J, Walsemann G, Grotzinger J, Kremmer E, Mehraein Y, Mertsching J, Kraft R, Austen M, Luscher-Firzlaff J, Luscher B. PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation. Oncogene. 2005 Mar 17;24(12):1982-93. PMID:15674325 doi:https://dx.doi.org/1208410
↑ Chou HY, Chou HT, Lee SC. CDK-dependent activation of poly(ADP-ribose) polymerase member 10 (PARP10). J Biol Chem. 2006 Jun 2;281(22):15201-7. Epub 2006 Feb 2. PMID:16455663 doi:https://dx.doi.org/10.1074/jbc.M506745200
↑ Thorsell AG, Ekblad T, Karlberg T, Low M, Pinto AF, Tresaugues L, Moche M, Cohen MS, Schuler H. Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors. J Med Chem. 2016 Dec 21. PMID:28001384

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Yu M, Schreek S, Cerni C, Schamberger C, Lesniewicz K, Poreba E, Vervoorts J, Walsemann G, Grotzinger J, Kremmer E, Mehraein Y, Mertsching J, Kraft R, Austen M, Luscher-Firzlaff J, Luscher B. PARP-10, a novel Myc-interacting protein with poly(ADP-ribose) polymerase activity, inhibits transformation. Oncogene. 2005 Mar 17;24(12):1982-93. PMID:15674325 doi:https://dx.doi.org/1208410

[2] Chou HY, Chou HT, Lee SC. CDK-dependent activation of poly(ADP-ribose) polymerase member 10 (PARP10). J Biol Chem. 2006 Jun 2;281(22):15201-7. Epub 2006 Feb 2. PMID:16455663 doi:https://dx.doi.org/10.1074/jbc.M506745200

[3] Thorsell AG, Ekblad T, Karlberg T, Low M, Pinto AF, Tresaugues L, Moche M, Cohen MS, Schuler H. Structural Basis for Potency and Promiscuity in Poly(ADP-ribose) Polymerase (PARP) and Tankyrase Inhibitors. J Med Chem. 2016 Dec 21. PMID:28001384

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
 ==Human PARP10 (ARTD10), catalytic fragment in complex with PARP inhibitor Veliparib==
-<StructureSection load='5lx6' size='340' side='right' caption='[[5lx6]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
+<StructureSection load='5lx6' size='340' side='right'caption='[[5lx6]], [[Resolution|resolution]] 1.25&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5lx6]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LX6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5LX6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5lx6]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5LX6 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5LX6 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=78P:(2R)-2-(7-CARBAMOYL-1H-BENZIMIDAZOL-2-YL)-2-METHYLPYRROLIDINIUM'>78P</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=78P:(2R)-2-(7-CARBAMOYL-1H-BENZIMIDAZOL-2-YL)-2-METHYLPYRROLIDINIUM'>78P</scene></td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PARP10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/NAD(+)_ADP-ribosyltransferase NAD(+) ADP-ribosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.30 2.4.2.30] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5lx6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lx6 OCA], [http://pdbe.org/5lx6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lx6 RCSB], [http://www.ebi.ac.uk/pdbsum/5lx6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lx6 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5lx6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lx6 OCA], [http://pdbe.org/5lx6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lx6 RCSB], [http://www.ebi.ac.uk/pdbsum/5lx6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lx6 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 5lx6" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Poly(ADP-ribose) polymerase 3D structures|Poly(ADP-ribose) polymerase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Karlberg, T]]
 [[Category: Schuler, H]]

5lx6: Difference between revisions

Revision as of 10:53, 12 August 2020

Human PARP10 (ARTD10), catalytic fragment in complex with PARP inhibitor Veliparib

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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