4Y3Y

Endothiapepsin in complex with fragment B42

Summary for 4Y3Y

• Entry DOI: 10.2210/pdb4y3y/pdb
• Related: 3PLL 4Y35 4Y36 4Y37 4Y38 4Y39 4Y3A 4Y3D 4Y3E 4Y3F 4Y3G 4Y3H 4Y3J 4Y3L 4Y3M 4Y3P 4Y3Q 4Y3R 4Y3S 4Y3T 4Y3W 4Y3X 4Y3Y 4Y3Z 4Y41 4Y43 4Y44 4Y45 4Y47 4Y48 4Y4A 4Y4B 4Y4C 4Y4D 4Y4E 4Y4G 4Y4J 4Y4T 4Y4U 4Y4W 4Y4X 4Y4Z 4Y50 4Y51 4Y53 4Y54 4Y56 4Y57 4Y58 4Y5A 4Y5B 4Y5C 4Y5E 4Y5G 4Y5K 4Y5L 4Y5M 4Y5N 4Y5P 4YCK 4YCT 4YCY 4YD3 4YD4 4YD5 4YD6 4YD7
• Descriptor: Endothiapepsin, GLYCEROL, ACETATE ION, ... (6 entities in total)
• Functional Keywords: fragment screening, aspartic protease inhibition, hydrolase
• Biological source: Cryphonectria parasitica (Chesnut blight fungus)
• Total number of polymer chains: 1
• Total formula weight: 34822.13

Authors

Huschmann, F.U.,Linnik, J.,Weiss, M.S.,Mueller, U. (deposition date: 2015-02-10, release date: 2016-02-17, Last modification date: 2024-01-10)

Primary citation

Huschmann, F.U.,Linnik, J.,Sparta, K.,Uhlein, M.,Wang, X.,Metz, A.,Schiebel, J.,Heine, A.,Klebe, G.,Weiss, M.S.,Mueller, U.
Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library.
Acta Crystallogr.,Sect.F, 72:346-355, 2016

PubMed Abstract: Crystallographic screening of the binding of small organic compounds (termed fragments) to proteins is increasingly important for medicinal chemistry-oriented drug discovery. To enable such experiments in a widespread manner, an affordable 96-compound library has been assembled for fragment screening in both academia and industry. The library is selected from already existing protein-ligand structures and is characterized by a broad ligand diversity, including buffer ingredients, carbohydrates, nucleotides, amino acids, peptide-like fragments and various drug-like organic compounds. When applied to the model protease endothiapepsin in a crystallographic screening experiment, a hit rate of nearly 10% was obtained. In comparison to other fragment libraries and considering that no pre-screening was performed, this hit rate is remarkably high. This demonstrates the general suitability of the selected compounds for an initial fragment-screening campaign. The library composition, experimental considerations and time requirements for a complete crystallographic fragment-screening campaign are discussed as well as the nine fully refined obtained endothiapepsin-fragment structures. While most of the fragments bind close to the catalytic centre of endothiapepsin in poses that have been observed previously, two fragments address new sites on the protein surface. ITC measurements show that the fragments bind to endothiapepsin with millimolar affinity.

PubMed: 27139825
DOI: 10.1107/S2053230X16004623

Experimental method

X-RAY DIFFRACTION (1.346 Å)