7zus: Difference between revisions

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-'''Unreleased structure'''
-The entry 7zus is ON HOLD  until Paper Publication
+==Crystal structure of ternary complex of Pol theta polymerase domain==
+<StructureSection load='7zus' size='340' side='right'caption='[[7zus]], [[Resolution|resolution]] 2.26&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7zus]] is a 9 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZUS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZUS FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DDG:2,3-DIDEOXY-GUANOSINE-5-MONOPHOSPHATE'>DDG</scene>, <scene name='pdbligand=DG3:2-3-DIDEOXYGUANOSINE-5-TRIPHOSPHATE'>DG3</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=7zus FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zus OCA], [https://pdbe.org/7zus PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zus RCSB], [https://www.ebi.ac.uk/pdbsum/7zus PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zus ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DPOLQ_HUMAN DPOLQ_HUMAN] Has a DNA polymerase activity on nicked double-stranded DNA and on a singly primed DNA template. The enzyme activity is resistant to aphidicolin, and inhibited by dideoxynucleotides. Exhibites a single-stranded DNA-dependent ATPase activity. Could be involved in the repair of interstrand cross-links.<ref>PMID:14576298</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Human DNA polymerase theta (Poltheta), which is essential for microhomology-mediated DNA double strand break repair, has been proposed as an attractive target for the treatment of BRCA deficient and other DNA repair pathway defective cancers. As previously reported, we recently identified the first selective small molecule Poltheta in vitro probe, 22 (ART558), which recapitulates the phenotype of Poltheta loss, and in vivo probe, 43 (ART812), which is efficacious in a model of PARP inhibitor resistant TNBC in vivo. Here we describe the discovery, biochemical and biophysical characterization of these probes including small molecule ligand co-crystal structures with Poltheta. The crystallographic data provides a basis for understanding the unique mechanism of inhibition of these compounds which is dependent on stabilization of a "closed" enzyme conformation. Additionally, the structural biology platform provided a basis for rational optimization based primarily on reduced ligand conformational flexibility.
-Authors:
+Discovery, Characterization, and Structure-Based Optimization of Small-Molecule In Vitro and In Vivo Probes for Human DNA Polymerase Theta.,Stockley ML, Ferdinand A, Benedetti G, Blencowe P, Boyd SM, Calder M, Charles MD, Edwardes LV, Ekwuru T, Finch H, Galbiati A, Geo L, Grande D, Grinkevich V, Holliday ND, Krajewski WW, MacDonald E, Majithiya JB, McCarron H, McWhirter CL, Patel V, Pedder C, Rajendra E, Ranzani M, Rigoreau LJM, Robinson HMR, Schaedler T, Sirina J, Smith GCM, Swarbrick ME, Turnbull AP, Willis S, Heald RA J Med Chem. 2022 Oct 6. doi: 10.1021/acs.jmedchem.2c01142. PMID:36200480<ref>PMID:36200480</ref>
-Description:
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 7zus" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Synthetic construct]]
+[[Category: Charles M]]
+[[Category: Heald RA]]
+[[Category: Krajewski WW]]
+[[Category: Stockley M]]
+[[Category: Turnbull AP]]
+[[Category: Willis S]]