7flp: Difference between revisions
Jump to navigation
Jump to search
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7flp]] 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=7FLP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FLP FirstGlance]. <br> | <table><tr><td colspan='2'>[[7flp]] 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=7FLP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FLP FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UYY:2-methoxybenzamide'>UYY</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]] 1.58Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UYY:2-methoxybenzamide'>UYY</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=7flp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7flp OCA], [https://pdbe.org/7flp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7flp RCSB], [https://www.ebi.ac.uk/pdbsum/7flp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7flp 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=7flp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7flp OCA], [https://pdbe.org/7flp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7flp RCSB], [https://www.ebi.ac.uk/pdbsum/7flp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7flp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| Line 13: | Line 14: | ||
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 7flp" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7flp" 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 13:25, 22 May 2024
PanDDA analysis group deposition -- Aar2/RNaseH in complex with fragment P05F11 from the F2X-Universal LibraryPanDDA analysis group deposition -- Aar2/RNaseH in complex with fragment P05F11 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
|
| ||||||||||||||||||