PDBsum entry 5p5o

Hydrolase

PDB id: 5p5o

Contents

Protein chain

330 a.a.

Waters ×255

PDB id:

5p5o

Name:

Hydrolase

Title:

Automated refinement of diffraction data obtained from an endothiapepsin crystal treated with fragment 249

Structure:

Endothiapepsin. Chain: a. Ec: 3.4.23.22

Source:

Cryphonectria parasitica. Organism_taxid: 5116

Resolution:

1.20Å R-factor: 0.122 R-free: 0.137

Authors:

J.Schiebel,A.Heine,G.Klebe

Key ref:

J.Schiebel et al. (2016). High-Throughput Crystallography: Reliable and Efficient Identification of Fragment Hits. Structure, 24, 1398-1409. PubMed id: 27452405 DOI: 10.1016/j.str.2016.06.010

Date:

28-Jun-16 Release date: 03-Aug-16

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.2016.06.010

Structure 24:1398-1409 (2016)

PubMed id: 27452405

High-Throughput Crystallography: Reliable and Efficient Identification of Fragment Hits.

J.Schiebel, S.G.Krimmer, K.Röwer, A.Knörlein, X.Wang, A.Y.Park, M.Stieler, F.R.Ehrmann, K.Fu, N.Radeva, M.Krug, F.U.Huschmann, S.Glöckner, M.S.Weiss, U.Mueller, G.Klebe, A.Heine.

ABSTRACT

Today the identification of lead structures for drug development often starts from small fragment-like molecules raising the chances to find compounds that successfully pass clinical trials. At the heart of the screening for fragments binding to a specific target, crystallography delivers structural information essential for subsequent drug design. While it is common to search for bound ligands in electron densities calculated directly after an initial refinement cycle, we raise the important question whether this strategy is viable for fragments characterized by low affinities. Here, we describe and provide a collection of high-quality diffraction data obtained from 364 protein crystals treated with diverse fragments. Subsequent data analysis showed that ∼25% of all hits would have been missed without further refining the resulting structures. To enable fast and reliable hit identification, we have designed an automated refinement pipeline that will inspire the development of optimized tools facilitating the successful application of fragment-based methods.