4pjv
From Proteopedia
(Difference between revisions)
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| - | ''' | + | ==Structure of PARP2 catalytic domain bound to inhibitor BMN 673== |
| + | <StructureSection load='4pjv' size='340' side='right' caption='[[4pjv]], [[Resolution|resolution]] 2.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4pjv]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PJV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PJV FirstGlance]. <br> | ||
| + | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2YQ:(8S,9R)-5-FLUORO-8-(4-FLUOROPHENYL)-9-(1-METHYL-1H-1,2,4-TRIAZOL-5-YL)-2,7,8,9-TETRAHYDRO-3H-PYRIDO[4,3,2-DE]PHTHALAZIN-3-ONE'>2YQ</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene><br> | ||
| + | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pjt|4pjt]]</td></tr> | ||
| + | <tr><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><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pjv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pjv OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pjv RCSB], [http://www.ebi.ac.uk/pdbsum/4pjv PDBsum]</span></td></tr> | ||
| + | <table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Poly(ADP-ribose) polymerases 1 and 2 (PARP1 and PARP2), which are involved in DNA damage response, are targets of anticancer therapeutics. BMN 673 is a novel PARP1/2 inhibitor with substantially increased PARP-mediated tumor cytotoxicity and is now in later-stage clinical development for BRCA-deficient breast cancers. In co-crystal structures, BMN 673 is anchored to the nicotinamide-binding pocket via an extensive network of hydrogen-bonding and pi-stacking interactions, including those mediated by active-site water molecules. The novel di-branched scaffold of BMN 673 extends the binding interactions towards the outer edges of the pocket, which exhibit the least sequence homology among PARP enzymes. The crystallographic structural analyses reported here therefore not only provide critical insights into the molecular basis for the exceptionally high potency of the clinical development candidate BMN 673, but also new opportunities for increasing inhibitor selectivity. | ||
| - | + | Structural basis for the inhibition of poly(ADP-ribose) polymerases 1 and 2 by BMN 673, a potent inhibitor derived from dihydropyridophthalazinone.,Aoyagi-Scharber M, Gardberg AS, Yip BK, Wang B, Shen Y, Fitzpatrick PA Acta Crystallogr F Struct Biol Commun. 2014 Sep 1;70(Pt 9):1143-9. doi:, 10.1107/S2053230X14015088. Epub 2014 Aug 29. PMID:25195882<ref>PMID:25195882</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | == References == | |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Aoyagi-Scharber, M.]] | ||
| + | [[Category: Edwards, T L.]] | ||
| + | [[Category: Gardberg, A S.]] | ||
| + | [[Category: Complex]] | ||
| + | [[Category: Inhibitor]] | ||
| + | [[Category: Parp2]] | ||
Revision as of 10:24, 24 September 2014
Structure of PARP2 catalytic domain bound to inhibitor BMN 673
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