4iqu
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4iqu]] is a 1 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=4IQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IQU FirstGlance]. <br> | <table><tr><td colspan='2'>[[4iqu]] is a 1 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=4IQU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4IQU FirstGlance]. <br> | ||
| - | </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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</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=4iqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iqu OCA], [https://pdbe.org/4iqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iqu RCSB], [https://www.ebi.ac.uk/pdbsum/4iqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iqu ProSAT]</span></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=4iqu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4iqu OCA], [https://pdbe.org/4iqu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4iqu RCSB], [https://www.ebi.ac.uk/pdbsum/4iqu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4iqu ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == 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. | [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. | ||
| - | + | ==See Also== | |
| - | + | *[[DNA polymerase 3D structures|DNA polymerase 3D structures]] | |
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Tdt core in complex with inhibitor (2Z,5E)-6-[4-(4-fluorobenzoyl)-1H-pyrrol-2-yl]-2-hydroxy-4-oxohexa-2,5-dienoic acid
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