4tya: Difference between revisions

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==An Ligand-observed Mass Spectrometry-based Approach Integrated into the Fragment Based Lead Discovery Pipeline==
==An Ligand-observed Mass Spectrometry-based Approach Integrated into the Fragment Based Lead Discovery Pipeline==
<StructureSection load='4tya' size='340' side='right' caption='[[4tya]], [[Resolution|resolution]] 2.94&Aring;' scene=''>
<StructureSection load='4tya' size='340' side='right'caption='[[4tya]], [[Resolution|resolution]] 2.94&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4tya]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TYA OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4TYA FirstGlance]. <br>
<table><tr><td colspan='2'>[[4tya]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Hepacivirus_C Hepacivirus C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4TYA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4TYA FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=3AE:4-(TRIFLUOROMETHYL)BENZOIC+ACID'>3AE</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]] 2.94&#8491;</td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4txf|4txf]], [[4txs|4txs]], [[4ty8|4ty8]], [[4ty9|4ty9]], [[4tyb|4tyb]]</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3AE:4-(TRIFLUOROMETHYL)BENZOIC+ACID'>3AE</scene></td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA-directed_RNA_polymerase RNA-directed RNA polymerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.48 2.7.7.48] </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=4tya FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tya OCA], [https://pdbe.org/4tya PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4tya RCSB], [https://www.ebi.ac.uk/pdbsum/4tya PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4tya ProSAT]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4tya FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4tya OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4tya RCSB], [http://www.ebi.ac.uk/pdbsum/4tya PDBsum]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Function ==
== Publication Abstract from PubMed ==
[https://www.uniprot.org/uniprot/D0PY27_9HEPC D0PY27_9HEPC]
In fragment-based lead discovery (FBLD), a cascade combining multiple orthogonal technologies is required for reliable detection and characterization of fragment binding to the target. Given the limitations of the mainstream screening techniques, we presented a ligand-observed mass spectrometry approach to expand the toolkits and increase the flexibility of building a FBLD pipeline especially for tough targets. In this study, this approach was integrated into a FBLD program targeting the HCV RNA polymerase NS5B. Our ligand-observed mass spectrometry analysis resulted in the discovery of 10 hits from a 384-member fragment library through two independent screens of complex cocktails and a follow-up validation assay. Moreover, this MS-based approach enabled quantitative measurement of weak binding affinities of fragments which was in general consistent with SPR analysis. Five out of the ten hits were then successfully translated to X-ray structures of fragment-bound complexes to lay a foundation for structure-based inhibitor design. With distinctive strengths in terms of high capacity and speed, minimal method development, easy sample preparation, low material consumption and quantitative capability, this MS-based assay is anticipated to be a valuable addition to the repertoire of current fragment screening techniques.
 
A ligand-observed mass spectrometry approach integrated into the fragment based lead discovery pipeline.,Chen X, Qin S, Chen S, Li J, Li L, Wang Z, Wang Q, Lin J, Yang C, Shui W Sci Rep. 2015 Feb 10;5:8361. doi: 10.1038/srep08361. PMID:25666181<ref>PMID:25666181</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: RNA-directed RNA polymerase]]
[[Category: Hepacivirus C]]
[[Category: Chen, S]]
[[Category: Large Structures]]
[[Category: Chen, X]]
[[Category: Chen S]]
[[Category: Lin, J]]
[[Category: Chen X]]
[[Category: Qin, S]]
[[Category: Lin J]]
[[Category: Shui, W]]
[[Category: Qin S]]
[[Category: Yang, C]]
[[Category: Shui W]]
[[Category: Inhibitor]]
[[Category: Yang C]]
[[Category: Ns5b]]
[[Category: Transferase-transferase inhibitor complex]]

Latest revision as of 12:00, 20 March 2024

An Ligand-observed Mass Spectrometry-based Approach Integrated into the Fragment Based Lead Discovery PipelineAn Ligand-observed Mass Spectrometry-based Approach Integrated into the Fragment Based Lead Discovery Pipeline

Structural highlights

4tya is a 4 chain structure with sequence from Hepacivirus C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.94Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

D0PY27_9HEPC

4tya, resolution 2.94Å

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