4ZEA
Endothiapepsin in complex with fragment B91
Summary for 4ZEA
| Entry DOI | 10.2210/pdb4zea/pdb |
| Related | 3PGI |
| Descriptor | Endothiapepsin, DIMETHYL SULFOXIDE, GLYCEROL, ... (7 entities in total) |
| Functional Keywords | fragment screening, hydrolase, inhibition |
| Biological source | Cryphonectria parasitica (Chesnut blight fungus) |
| Total number of polymer chains | 1 |
| Total formula weight | 35560.98 |
| Authors | Huschmann, F.U.,Linnik, J.,Weiss, M.S.,Mueller, U. (deposition date: 2015-04-20, release date: 2016-05-04, Last modification date: 2024-11-13) |
| 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 Cited by 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: 27139825DOI: 10.1107/S2053230X16004623 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.2 Å) |
Structure validation
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