4n4t

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
{{STRUCTURE_4n4t| PDB=4n4t | SCENE= }}
+
==Co-crystal structure of tankyrase 1 with compound 3 [(4S)-3-{4-[6-amino-5-(pyrimidin-2-yl)pyridin-3-yl]phenyl}-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one]==
-
===Co-crystal structure of tankyrase 1 with compound 3 [(4S)-3-{4-[6-amino-5-(pyrimidin-2-yl)pyridin-3-yl]phenyl}-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one]===
+
<StructureSection load='4n4t' size='340' side='right' caption='[[4n4t]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
 +
== Structural highlights ==
 +
<table><tr><td colspan='2'>[[4n4t]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N4T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4N4T FirstGlance]. <br>
 +
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=2GV:(4S)-3-{4-[6-AMINO-5-(PYRIMIDIN-2-YL)PYRIDIN-3-YL]PHENYL}-5,5-DIMETHYL-4-PHENYL-1,3-OXAZOLIDIN-2-ONE'>2GV</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
 +
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k4f|4k4f]], [[4n3r|4n3r]], [[4n4v|4n4v]]</td></tr>
 +
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Tnks, Tnks1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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=4n4t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4n4t OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4n4t RCSB], [http://www.ebi.ac.uk/pdbsum/4n4t PDBsum]</span></td></tr>
 +
<table>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Aberrant activation of the Wnt pathway has been implicated in the development and formation of many cancers. TNKS inhibition has been shown to antagonize Wnt signaling via Axin stabilization in APC mutant colon cancer cell lines. We employed structure-based design to identify a series of 2-aminopyridine oxazolidinones as potent and selective TNKS inhibitors. These compounds exhibited good enzyme and cell potency as well as selectivity over other PARP isoforms. Co-crystal structures of these 2-aminopyridine oxazolidinones complexed to TNKS reveal an induced-pocket binding mode that does not involve interactions with the nicotinamide binding pocket. Oral dosing of lead compounds 3 and 4 resulted in significant effects on several Wnt-pathway biomarkers in a three day DLD-1 mouse tumor PD model.
-
==Function==
+
Structure-based design of 2-aminopyridine oxazolidinones as potent and selective tankyrase inhibitors.,Huang H, Guzman-Perez A, Acquaviva L, Berry V, Bregman H, Dovey J, Gunaydin H, Huang X, Huang L, Saffran D, Serafino R, Schneider S, Wilson C, DiMauro EF ACS Med Chem Lett. 2013 Oct 21;4(12):1218-23. doi: 10.1021/ml4003315. eCollection, 2013 Dec 12. PMID:24900633<ref>PMID:24900633</ref>
-
[[http://www.uniprot.org/uniprot/TNKS1_MOUSE TNKS1_MOUSE]] Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1 (By similarity).
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[4n4t]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4N4T OCA].
+
</div>
 +
== References ==
 +
<references/>
 +
__TOC__
 +
</StructureSection>
 +
[[Category: Lk3 transgenic mice]]
[[Category: Huang, X.]]
[[Category: Huang, X.]]
[[Category: Inhibitor]]
[[Category: Inhibitor]]

Revision as of 06:14, 2 July 2014

Co-crystal structure of tankyrase 1 with compound 3 [(4S)-3-{4-[6-amino-5-(pyrimidin-2-yl)pyridin-3-yl]phenyl}-5,5-dimethyl-4-phenyl-1,3-oxazolidin-2-one]

4n4t, resolution 2.31Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4n4t"
Views
Personal tools
Navigation
Toolbox