7fpc: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7fpc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FPC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FPC FirstGlance]. <br> | <table><tr><td colspan='2'>[[7fpc]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7FPC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FPC FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=W4W:({2-[(2S)-2-ethylpiperidin-1-yl]-2-oxoethyl}sulfanyl)acetonitrile'>W4W</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]] 1.55Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=W4W:({2-[(2S)-2-ethylpiperidin-1-yl]-2-oxoethyl}sulfanyl)acetonitrile'>W4W</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=7fpc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fpc OCA], [https://pdbe.org/7fpc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fpc RCSB], [https://www.ebi.ac.uk/pdbsum/7fpc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fpc 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=7fpc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fpc OCA], [https://pdbe.org/7fpc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fpc RCSB], [https://www.ebi.ac.uk/pdbsum/7fpc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fpc ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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The identification of starting points for compound development is one of the key steps in early-stage drug discovery. Information-rich techniques such as crystallographic fragment screening can potentially increase the efficiency of this step by providing the structural information of the binding mode of the ligands in addition to the mere binding information. Here, we present the crystallographic screening of our 1000-plus-compound F2X-Universal Library against the complex of the yeast spliceosomal Prp8 RNaseH-like domain and the snRNP assembly factor Aar2. The observed 269 hits are distributed over 10 distinct binding sites on the surface of the protein-protein complex. Our work shows that hit clusters from large-scale crystallographic fragment screening campaigns identify known interaction sites with other proteins and suggest putative additional interaction sites. Furthermore, the inherent binding pose validation within the hit clusters may accelerate downstream compound optimization. | The identification of starting points for compound development is one of the key steps in early-stage drug discovery. Information-rich techniques such as crystallographic fragment screening can potentially increase the efficiency of this step by providing the structural information of the binding mode of the ligands in addition to the mere binding information. Here, we present the crystallographic screening of our 1000-plus-compound F2X-Universal Library against the complex of the yeast spliceosomal Prp8 RNaseH-like domain and the snRNP assembly factor Aar2. The observed 269 hits are distributed over 10 distinct binding sites on the surface of the protein-protein complex. Our work shows that hit clusters from large-scale crystallographic fragment screening campaigns identify known interaction sites with other proteins and suggest putative additional interaction sites. Furthermore, the inherent binding pose validation within the hit clusters may accelerate downstream compound optimization. | ||
Large-Scale Crystallographic Fragment Screening Expedites Compound Optimization and Identifies Putative Protein-Protein Interaction Sites.,Barthel T, Wollenhaupt J, Lima GMA, Wahl MC, Weiss MS J Med Chem. 2022 | Large-Scale Crystallographic Fragment Screening Expedites Compound Optimization and Identifies Putative Protein-Protein Interaction Sites.,Barthel T, Wollenhaupt J, Lima GMA, Wahl MC, Weiss MS J Med Chem. 2022 Nov 10;65(21):14630-14641. doi: 10.1021/acs.jmedchem.2c01165. , Epub 2022 Oct 19. PMID:36260741<ref>PMID:36260741</ref> | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 7fpc" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7fpc" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||