PDBsum entry 5rdc

Hydrolase

PDB id: 5rdc

Contents

Protein chain

330 a.a.

Ligands

GOL ×3

ACT ×2

PGE

PG4

PEG

Metals

_NA

Waters ×341

PDB id:

5rdc

Name:

Hydrolase

Title:

Pandda analysis group deposition -- endothiapepsin ground state model 34

Structure:

Endothiapepsin. Chain: a. Synonym: aspartate protease. Ec: 3.4.23.22

Source:

Cryphonectria parasitica. Chestnut blight fungus. Organism_taxid: 5116

Resolution:

1.02Å R-factor: 0.162 R-free: 0.162

Authors:

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

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:

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

Protein chain

P11838  (CARP_CRYPA) -  Endothiapepsin from Cryphonectria parasitica

Seq: 419 a.a.

Struc: 330 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.23.22 - endothiapepsin.
• Reaction: Hydrolysis of proteins with broad specificity similar to that of pepsin A, preferring hydrophobic residues at P1 and P1', but does not cleave 14-Ala-|-Leu-15 in the B chain of insulin or Z-Glu-Tyr. Clots milk.

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.