5ST7

PanDDA analysis group deposition -- Aar2/RNaseH in complex with fragment P02E03 from the F2X-Universal Library

5ST7 の概要

• エントリーDOI: 10.2210/pdb5st7/pdb
• Group deposition: PanDDA analysis group deposition (G_1002241)
• 分子名称: Pre-mRNA-splicing factor 8, A1 cistron-splicing factor AAR2, (3R)-3-(benzylamino)oxolane-3-carboxylic acid, ... (4 entities in total)
• 機能のキーワード: fragmax, fragmaxapp, fragment screening, rnaseh like domain, u5 snrnp assembly, splicing
• 由来する生物種: Saccharomyces cerevisiae S288C; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 65932.20

構造登録者

Barthel, T.,Wollenhaupt, J.,Lima, G.M.A.,Wahl, M.C.,Weiss, M.S. (登録日: 2022-08-26, 公開日: 2022-11-02, 最終更新日: 2024-05-22)

主引用文献

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.
J.Med.Chem., 65:14630-14641, 2022

PubMed Abstract: 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.

PubMed: 36260741
DOI: 10.1021/acs.jmedchem.2c01165

実験手法

X-RAY DIFFRACTION (1.46 Å)