5r1h

PanDDA analysis group deposition -- Auto-refined data of Aar2/RNaseH for ground state model 32, DMSO-freePanDDA analysis group deposition -- Auto-refined data of Aar2/RNaseH for ground state model 32, DMSO-free

Structural highlights

5r1h is a 2 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	PRP8, DBF3, DNA39, RNA8, SLT21, USA2, YHR165C (Baker's yeast), AAR2, YBL074C, YBL06.06, YBL0611 (Baker's yeast)
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] [AAR2_YEAST] Involved in splicing pre-mRNA of the A1 cistron and other genes that are important for cell growth.

Publication Abstract from PubMed

Crystallographic fragment screening (CFS) provides excellent starting points for projects concerned with drug discovery or biochemical tool compound development. One of the fundamental prerequisites for effective CFS is the availability of a versatile fragment library. Here, we report on the assembly of the 1,103-compound F2X-Universal Library and its 96-compound sub-selection, the F2X-Entry Screen. Both represent the available fragment chemistry and are highly diverse in terms of their 3D-pharmacophore variations. Validation of the F2X-Entry Screen in CFS campaigns using endothiapepsin and the Aar2/RNaseH complex yielded hit rates of 30% and 21%, respectively, and revealed versatile binding sites. Dry presentation of the libraries allows CFS campaigns to be carried out with or without the co-solvent DMSO present. Most of the hits in our validation campaigns could be reproduced also in the absence of DMSO. Consequently, CFS can be carried out more efficiently and for a wider range of conditions and targets.

F2X-Universal and F2X-Entry: Structurally Diverse Compound Libraries for Crystallographic Fragment Screening.,Wollenhaupt J, Metz A, Barthel T, Lima GMA, Heine A, Mueller U, Klebe G, Weiss MS Structure. 2020 Jun 2;28(6):694-706.e5. doi: 10.1016/j.str.2020.04.019. Epub 2020, May 14. PMID:32413289^[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
↑ Wollenhaupt J, Metz A, Barthel T, Lima GMA, Heine A, Mueller U, Klebe G, Weiss MS. F2X-Universal and F2X-Entry: Structurally Diverse Compound Libraries for Crystallographic Fragment Screening. Structure. 2020 Jun 2;28(6):694-706.e5. doi: 10.1016/j.str.2020.04.019. Epub 2020, May 14. PMID:32413289 doi:http://dx.doi.org/10.1016/j.str.2020.04.019

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] 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

[3] 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

[4] 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

[5] Wollenhaupt J, Metz A, Barthel T, Lima GMA, Heine A, Mueller U, Klebe G, Weiss MS. F2X-Universal and F2X-Entry: Structurally Diverse Compound Libraries for Crystallographic Fragment Screening. Structure. 2020 Jun 2;28(6):694-706.e5. doi: 10.1016/j.str.2020.04.019. Epub 2020, May 14. PMID:32413289 doi:http://dx.doi.org/10.1016/j.str.2020.04.019

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