6e53: Difference between revisions

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-'''Unreleased structure'''
-The entry 6e53 is ON HOLD
+==Structure of TERT in complex with a novel telomerase inhibitor==
+<StructureSection load='6e53' size='340' side='right'caption='[[6e53]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6e53]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Tribolium_castaneum Tribolium castaneum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E53 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E53 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]] 2.8&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HUV:methyl+1-{2-deoxy-5-O-[(S)-hydroxy{[(S)-hydroxy(phosphonooxy)phosphoryl]oxy}phosphoryl]-alpha-D-erythro-pentofuranosyl}-1H-indole-5-carboxylate'>HUV</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=6e53 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e53 OCA], [https://pdbe.org/6e53 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e53 RCSB], [https://www.ebi.ac.uk/pdbsum/6e53 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e53 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/Q0QHL8_TRICA Q0QHL8_TRICA]
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Telomerase, a unique reverse transcriptase that specifically extends the ends of linear chromosomes, is up-regulated in the vast majority of cancer cells. Here, we show that an indole nucleotide analog, 5-methylcarboxyl-indolyl-2'-deoxyriboside 5'-triphosphate (5-MeCITP), functions as an inhibitor of telomerase activity. The crystal structure of 5-MeCITP bound to the Tribolium castaneum telomerase reverse transcriptase reveals an atypical interaction, in which the nucleobase is flipped in the active site. In this orientation, the methoxy group of 5-MeCITP extends out of the canonical active site to interact with a telomerase-specific hydrophobic pocket formed by motifs 1 and 2 in the fingers domain and T-motif in the RNA-binding domain of the telomerase reverse transcriptase. In vitro data show that 5-MeCITP inhibits telomerase with a similar potency as the clinically administered nucleoside analog reverse transcriptase inhibitor azidothymidine (AZT). In addition, cell-based studies show that treatment with the cell-permeable nucleoside counterpart of 5-MeCITP leads to telomere shortening in telomerase-positive cancer cells, while resulting in significantly lower cytotoxic effects in telomerase-negative cell lines when compared with AZT treatment.
-Authors: Hernandez-Sanchez, W., Huang, W., Plucinsky, B., Garcia-Vazquez, N., Berdis, A.J., Skordalakes, E., Taylor, D.J.
+A non-natural nucleotide uses a specific pocket to selectively inhibit telomerase activity.,Hernandez-Sanchez W, Huang W, Plucinsky B, Garcia-Vazquez N, Robinson NJ, Schiemann WP, Berdis AJ, Skordalakes E, Taylor DJ PLoS Biol. 2019 Apr 5;17(4):e3000204. doi: 10.1371/journal.pbio.3000204., eCollection 2019 Apr. PMID:30951520<ref>PMID:30951520</ref>
-Description: Structure of TERT in complex with a novel telomerase inhibitor
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Huang, W]]
+<div class="pdbe-citations 6e53" style="background-color:#fffaf0;"></div>
-[[Category: Garcia-Vazquez, N]]
-[[Category: Hernandez-Sanchez, W]]
+==See Also==
-[[Category: Plucinsky, B]]
+*[[Telomerase 3D structures|Telomerase 3D structures]]
-[[Category: Berdis, A.J]]
+== References ==
-[[Category: Skordalakes, E]]
+<references/>
-[[Category: Taylor, D.J]]
+__TOC__
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Tribolium castaneum]]
+[[Category: Berdis AJ]]
+[[Category: Garcia-Vazquez N]]
+[[Category: Hernandez-Sanchez W]]
+[[Category: Huang W]]
+[[Category: Plucinsky B]]
+[[Category: Skordalakes E]]
+[[Category: Taylor DJ]]