View source for 4iqw


==Tdt core in complex with inhibitor (2Z,5E)-6-[4-(4-fluorobenzoyl)-1H-pyrrol-2-yl]-2-hydroxy-4-oxohexa-2,5-dienoic acid and ssDNA==
<StructureSection load='4iqw' size='340' side='right'caption='[[4iqw]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4iqw]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4IQW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IQW FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1FQ:(2Z,5E)-6-[4-(4-FLUOROBENZOYL)-1H-PYRROL-2-YL]-2-HYDROXY-4-OXOHEXA-2,5-DIENOIC+ACID'>1FQ</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</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=4iqw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iqw OCA], [https://pdbe.org/4iqw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iqw RCSB], [https://www.ebi.ac.uk/pdbsum/4iqw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iqw ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/TDT_MOUSE TDT_MOUSE] Template-independent DNA polymerase which catalyzes the random addition of deoxynucleoside 5'-triphosphate to the 3'-end of a DNA initiator. One of the in vivo functions of this enzyme is the addition of nucleotides at the junction (N region) of rearranged Ig heavy chain and T-cell receptor gene segments during the maturation of B- and T-cells.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Terminal deoxynucletidyl transferase (TdT) is overexpressed in some cancer types, where it might compete with pol mu driving the mutagenic repair of double strand breaks (DSBs) through the non homologous end joining (NHEJ) pathway. Here we report the discovery and characterization of pyrrolyl and indolyl diketo acids that specifically target TdT and behave as nucleotide-competitive inhibitors. These compounds show a selective toxicity towards MOLT-4 compared to HeLa cells that correlate well with in vitro selectivity for TdT. The binding site of two of these inhibitors was determined by co-crystallization with TdT, explaining why these compounds are competitive inhibitors of the deoxynucleotide triphosphate (dNTP). In addition, because of the observed dual localization of the phenyl substituent, these studies open the possibility to rationally design more potent compounds.

New Nucleotide-Competitive Non-Nucleoside Inhibitors of Terminal Deoxynucleotidyl Transferase: Discovery, Characterization and Crystal Structure in Complex with the Target.,Costi R, Cuzzucoli Crucitti G, Pescatori L, Messore A, Scipione L, Tortorella S, Amoroso A, Crespan E, Campiglia P, Maresca B, Novellino E, Gouge J, Delarue MH, Maga G, Di Santo R J Med Chem. 2013 Aug 22. PMID:23968551<ref>PMID:23968551</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 4iqw" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA polymerase 3D structures|DNA polymerase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Delarue M]]
[[Category: Gouge J]]