8szs: Difference between revisions
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==Cat DHX9 bound to GDP== | |||
<StructureSection load='8szs' size='340' side='right'caption='[[8szs]], [[Resolution|resolution]] 2.38Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8szs]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Felis_catus Felis catus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8SZS OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8SZS 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]] 2.38Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GDP:GUANOSINE-5-DIPHOSPHATE'>GDP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=8szs FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8szs OCA], [https://pdbe.org/8szs PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8szs RCSB], [https://www.ebi.ac.uk/pdbsum/8szs PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8szs ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/A0A337SGK2_FELCA A0A337SGK2_FELCA] | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
DHX9 is a DExH-box RNA helicase that utilizes hydrolysis of all four nucleotide triphosphates (NTPs) to power cycles of 3' to 5' directional movement to resolve and/or unwind double stranded RNA, DNA, and RNA/DNA hybrids, R-loops, triplex-DNA and G-quadraplexes. DHX9 activity is important for both viral amplification and maintaining genomic stability in cancer cells; therefore, it is a therapeutic target of interest for drug discovery efforts. Biochemical assays measuring ATP hydrolysis and oligonucleotide unwinding for DHX9 have been developed and characterized, and these assays can support high-throughput compound screening efforts under balanced conditions. Assay development efforts revealed DHX9 can use double stranded RNA with 18-mer poly(U) 3' overhangs and as well as significantly shorter overhangs at the 5' or 3' end as substrates. The enzymatic assays are augmented by a robust SPR assay for compound validation. A mechanism-derived inhibitor, GTPgammaS, was characterized as part of the validation of these assays and a crystal structure of GDP bound to cat DHX9 has been solved. In addition to enabling drug discovery efforts for DHX9, these assays may be extrapolated to other RNA helicases providing a valuable toolkit for this important target class. | |||
Development of assays to support identification and characterization of modulators of DExH-box helicase DHX9.,Gotur D, Case A, Liu J, Sickmier EA, Holt N, Knockenhauer KE, Yao S, Lee YT, Copeland RA, Buker SM, Boriack-Sjodin PA SLAS Discov. 2023 Aug 23:S2472-5552(23)00063-1. doi: 10.1016/j.slasd.2023.08.006. PMID:37625785<ref>PMID:37625785</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8szs" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Felis catus]] | |||
[[Category: Large Structures]] | |||
[[Category: Boriack-Sjodin PA]] | |||
[[Category: Lee Y-T]] | |||
[[Category: Sickmier EA]] | |||
