5R22

PanDDA analysis group deposition -- Endothiapepsin in complex with fragment F2X-Entry E11, DMSO-free

Summary for 5R22

• Entry DOI: 10.2210/pdb5r22/pdb
• Group deposition: PanDDA analysis of F2X-Entry Screen vs. Endothiapepsin, DMSO-free soaking (G_1002120)
• Descriptor: Endothiapepsin, [2-(morpholin-4-yl)-1,3-thiazol-5-yl]methanol (3 entities in total)
• Functional Keywords: hydrolase
• Biological source: Cryphonectria parasitica (Chestnut blight fungus)
• Total number of polymer chains: 1
• Total formula weight: 43478.92

Authors

Wollenhaupt, J.,Metz, A.,Barthel, T.,Lima, G.M.A.,Heine, A.,Mueller, U.,Klebe, G.,Weiss, M.S. (deposition date: 2020-02-13, release date: 2020-06-03, Last modification date: 2020-07-08)

Primary citation

Wollenhaupt, J.,Metz, A.,Barthel, T.,Lima, G.M.A.,Heine, A.,Mueller, U.,Klebe, G.,Weiss, M.S.
F2X-Universal and F2X-Entry: Structurally Diverse Compound Libraries for Crystallographic Fragment Screening.
Structure, 28:694-706.e5, 2020

PubMed Abstract: 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.

PubMed: 32413289
DOI: 10.1016/j.str.2020.04.019

Experimental method

X-RAY DIFFRACTION (1.098 Å)