5stm

From Proteopedia

(Difference between revisions)

Revision as of 07:03, 3 November 2022

PanDDA analysis group deposition -- Aar2/RNaseH in complex with fragment P03A03 from the F2X-Universal Library

Structural highlights

5stm is a 2 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4]

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^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Jackson SP, Lossky M, Beggs JD. Cloning of the RNA8 gene of Saccharomyces cerevisiae, detection of the RNA8 protein, and demonstration that it is essential for nuclear pre-mRNA splicing. Mol Cell Biol. 1988 Mar;8(3):1067-75. PMID:2835658
↑ Abovich N, Rosbash M. Cross-intron bridging interactions in the yeast commitment complex are conserved in mammals. Cell. 1997 May 2;89(3):403-12. PMID:9150140
↑ McPheeters DS, Muhlenkamp P. Spatial organization of protein-RNA interactions in the branch site-3' splice site region during pre-mRNA splicing in yeast. Mol Cell Biol. 2003 Jun;23(12):4174-86. PMID:12773561
↑ Yang K, Zhang L, Xu T, Heroux A, Zhao R. Crystal structure of the beta-finger domain of Prp8 reveals analogy to ribosomal proteins. Proc Natl Acad Sci U S A. 2008 Sep 16;105(37):13817-22. Epub 2008 Sep 8. PMID:18779563
↑ Barthel T, Wollenhaupt J, Lima GMA, Wahl MC, Weiss MS. Large-Scale Crystallographic Fragment Screening Expedites Compound Optimization and Identifies Putative Protein-Protein Interaction Sites. J Med Chem. 2022 Oct 19. doi: 10.1021/acs.jmedchem.2c01165. PMID:36260741 doi:http://dx.doi.org/10.1021/acs.jmedchem.2c01165

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5stm"

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5stm is ON HOLD
+==PanDDA analysis group deposition -- Aar2/RNaseH in complex with fragment P03A03 from the F2X-Universal Library==
+<StructureSection load='5stm' size='340' side='right'caption='[[5stm]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[5stm]] 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=5STM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5STM FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=W9I:5-bromo-2-hydrazinylpyridine'>W9I</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=5stm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5stm OCA], [https://pdbe.org/5stm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5stm RCSB], [https://www.ebi.ac.uk/pdbsum/5stm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5stm 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.
-Authors: Barthel, T., Wollenhaupt, J., Lima, G.M.A., Wahl, M.C., Weiss, M.S.
+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>
-Description: PanDDA analysis group deposition --Aar2/RNaseH in complex with fragment P03A03 from the F2X-Universal Library
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Wahl, M.C]]
+<div class="pdbe-citations 5stm" style="background-color:#fffaf0;"></div>
-[[Category: Lima, G.M.A]]
+== References ==
-[[Category: Weiss, M.S]]
+<references/>
-[[Category: Wollenhaupt, J]]
+__TOC__
-[[Category: Barthel, T]]
+</StructureSection>
+[[Category: Large Structures]]
+[[Category: Saccharomyces cerevisiae S288C]]
+[[Category: Barthel T]]
+[[Category: Lima GMA]]
+[[Category: Wahl MC]]
+[[Category: Weiss MS]]
+[[Category: Wollenhaupt J]]

5stm

From Proteopedia

Revision as of 07:03, 3 November 2022

PanDDA analysis group deposition -- Aar2/RNaseH in complex with fragment P03A03 from the F2X-Universal Library

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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