7fmv: Difference between revisions
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7fmv]] 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=7FMV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FMV FirstGlance]. <br> | <table><tr><td colspan='2'>[[7fmv]] 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=7FMV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FMV FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VQU:(2R,4S)-2-(pyridin-3-yl)-1,3-thiazolidine-4-carboxylic+acid'>VQU</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]] 1.61Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VQU:(2R,4S)-2-(pyridin-3-yl)-1,3-thiazolidine-4-carboxylic+acid'>VQU</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=7fmv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fmv OCA], [https://pdbe.org/7fmv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fmv RCSB], [https://www.ebi.ac.uk/pdbsum/7fmv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fmv 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=7fmv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fmv OCA], [https://pdbe.org/7fmv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fmv RCSB], [https://www.ebi.ac.uk/pdbsum/7fmv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fmv 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 7fmv" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7fmv" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Pre-mRNA splicing factors 3D structures|Pre-mRNA splicing factors 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
Latest revision as of 13:27, 22 May 2024
PanDDA analysis group deposition -- Aar2/RNaseH in complex with fragment P06E12 from the F2X-Universal LibraryPanDDA analysis group deposition -- Aar2/RNaseH in complex with fragment P06E12 from the F2X-Universal Library
Structural highlights
FunctionAAR2_YEAST Involved in splicing pre-mRNA of the A1 cistron and other genes that are important for cell growth. Publication Abstract from PubMedThe 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 Nov 10;65(21):14630-14641. doi: 10.1021/acs.jmedchem.2c01165. , Epub 2022 Oct 19. PMID:36260741[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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