7fld: Difference between revisions
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The | ==PanDDA analysis group deposition -- Aar2/RNaseH in complex with fragment P05B11 from the F2X-Universal Library== | ||
<StructureSection load='7fld' size='340' side='right'caption='[[7fld]], [[Resolution|resolution]] 1.51Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7fld]] 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=7FLD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7FLD FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=VQ2:[4-(diethylcarbamoyl)phenyl]boronic+acid'>VQ2</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=7fld FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7fld OCA], [https://pdbe.org/7fld PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7fld RCSB], [https://www.ebi.ac.uk/pdbsum/7fld PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7fld ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PRP8_YEAST PRP8_YEAST] Required for pre-spliceosome formation, which is the first step of pre-mRNA splicing. This protein is associated with snRNP U5. Has a role in branch site-3' splice site selection. Associates with the branch site-3' splice 3'-exon region. Also has a role in cell cycle.<ref>PMID:2835658</ref> <ref>PMID:9150140</ref> <ref>PMID:12773561</ref> <ref>PMID:18779563</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
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 Oct 19. doi: 10.1021/acs.jmedchem.2c01165. PMID:36260741<ref>PMID:36260741</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 7fld" style="background-color:#fffaf0;"></div> | ||
[[Category: Lima | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae S288C]] | |||
[[Category: Barthel T]] | |||
[[Category: Lima GMA]] | |||
[[Category: Wahl MC]] | |||
[[Category: Weiss MS]] | |||
[[Category: Wollenhaupt J]] | |||
Revision as of 10:06, 3 November 2022
PanDDA analysis group deposition -- Aar2/RNaseH in complex with fragment P05B11 from the F2X-Universal LibraryPanDDA analysis group deposition -- Aar2/RNaseH in complex with fragment P05B11 from the F2X-Universal Library
Structural highlights
FunctionPRP8_YEAST Required for pre-spliceosome formation, which is the first step of pre-mRNA splicing. This protein is associated with snRNP U5. Has a role in branch site-3' splice site selection. Associates with the branch site-3' splice 3'-exon region. Also has a role in cell cycle.[1] [2] [3] [4] 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 Oct 19. doi: 10.1021/acs.jmedchem.2c01165. PMID:36260741[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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