PDBsum entry 5r0c

Splicing

PDB id: 5r0c

Contents

Protein chains

237 a.a.

300 a.a.

Ligands

R8V

Waters ×123

PDB id:

5r0c

Name:

Splicing

Title:

Pandda analysis group deposition -- aar2/rnaseh in complex with fragment f2x-entry c08, dmso-free

Structure:

Pre-mRNA-splicing factor 8. Chain: a. Fragment: yprp8 rnaseh (unp residues 1836-2096). Engineered: yes. A1 cistron-splicing factor aar2. Chain: b. Fragment: gama - aar2(1-152) - sssss - aar2(171-317). Engineered: yes. Mutation: yes

Source:

Saccharomyces cerevisiae (strain atcc 204508 / s288c). Baker's yeast. Organism_taxid: 559292. Strain: atcc 204508 / s288c. Gene: prp8, dbf3, dna39, rna8, slt21, usa2, yhr165c. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: aar2, ybl074c, ybl06.06, ybl0611.

Resolution:

1.60Å R-factor: 0.206 R-free: 0.250

Authors:

J.Wollenhaupt,A.Metz,T.Barthel,G.M.A.Lima,A.Heine,U.Mueller,G.Klebe, M.S.Weiss

Key ref:

J.Wollenhaupt et al. (2020). F2X-Universal and F2X-Entry: Structurally Diverse Compound Libraries for Crystallographic Fragment Screening. Structure, 28, 694. PubMed id: 32413289 DOI: 10.1016/j.str.2020.04.019

Date:

30-Mar-20 Release date: 03-Jun-20

Protein chain

P33334  (PRP8_YEAST) -  Pre-mRNA-splicing factor 8 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 2413 a.a.

Struc: 237 a.a.*

Protein chain

P32357  (AAR2_YEAST) -  A1 cistron-splicing factor AAR2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 355 a.a.

Struc: 300 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1016/j.str.2020.04.019

Structure 28:694 (2020)

PubMed id: 32413289

F2X-Universal and F2X-Entry: Structurally Diverse Compound Libraries for Crystallographic Fragment Screening.

J.Wollenhaupt, A.Metz, T.Barthel, G.M.A.Lima, A.Heine, U.Mueller, G.Klebe, M.S.Weiss.

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.