7QM9
Endothiapepsin in complex with compound TL00150 at room-temperature (temperature ramping down structure 1)
Summary for 7QM9
| Entry DOI | 10.2210/pdb7qm9/pdb |
| Related | 7QLT 7QLU 7QLV 7QLW 7QLX 7QLY 7QLZ 7QM0 7QM1 7QM3 7QM4 7QM5 7QM6 7QM7 7QM8 7QMA 7QMB 7QMC 7QMD 7QME 7QMF 7QMG 7QMH 7QMI 7QMJ 7QMK 7QML 7QMM 7QMN 7QMO 7QMP 7QMQ 7QMR 7QMS 7QMT 7QMU 7QMV 7QMW 7QMX 7QMY 7QMZ 7QN0 7QN1 7QN2 7QN3 7QN4 |
| Descriptor | Endothiapepsin, [4-(trifluoromethyl)phenyl]methanamine, 1-METHOXY-2-[2-(2-METHOXY-ETHOXY]-ETHANE, ... (5 entities in total) |
| Functional Keywords | endopeptidase, hydrolase |
| Biological source | Cryphonectria parasitica (chestnut blight fungus) |
| Total number of polymer chains | 1 |
| Total formula weight | 43866.44 |
| Authors | Huang, C.Y.,Aumonier, S.,Wang, M. (deposition date: 2021-12-20, release date: 2022-08-17, Last modification date: 2024-11-13) |
| Primary citation | Huang, C.Y.,Aumonier, S.,Engilberge, S.,Eris, D.,Smith, K.M.L.,Leonarski, F.,Wojdyla, J.A.,Beale, J.H.,Buntschu, D.,Pauluhn, A.,Sharpe, M.E.,Metz, A.,Olieric, V.,Wang, M. Probing ligand binding of endothiapepsin by `temperature-resolved' macromolecular crystallography. Acta Crystallogr D Struct Biol, 78:964-974, 2022 Cited by PubMed Abstract: Continuous developments in cryogenic X-ray crystallography have provided most of our knowledge of 3D protein structures, which has recently been further augmented by revolutionary advances in cryoEM. However, a single structural conformation identified at cryogenic temperatures may introduce a fictitious structure as a result of cryogenic cooling artefacts, limiting the overview of inherent protein physiological dynamics, which play a critical role in the biological functions of proteins. Here, a room-temperature X-ray crystallographic method using temperature as a trigger to record movie-like structural snapshots has been developed. The method has been used to show how TL00150, a 175.15 Da fragment, undergoes binding-mode changes in endothiapepsin. A surprising fragment-binding discrepancy was observed between the cryo-cooled and physiological temperature structures, and multiple binding poses and their interplay with DMSO were captured. The observations here open up new promising prospects for structure determination and interpretation at physiological temperatures with implications for structure-based drug discovery. PubMed: 35916221DOI: 10.1107/S205979832200612X PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.79 Å) |
Structure validation
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