This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


4tya

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (09:00, 20 March 2024) (edit) (undo)
 
(2 intermediate revisions not shown.)
Line 1: Line 1:
==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 with sequence from [http://en.wikipedia.org/wiki/9hepc 9hepc]. 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://pdbe.org/4tya PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4tya RCSB], [http://www.ebi.ac.uk/pdbsum/4tya PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4tya ProSAT]</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>
+
-
<div class="pdbe-citations 4tya" style="background-color:#fffaf0;"></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]]
+

Current revision

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

PDB ID 4tya

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4tya"
Personal tools