5MNQ
Cationic trypsin in complex with a derivative of N-amidinopiperidine
Summary for 5MNQ
| Entry DOI | 10.2210/pdb5mnq/pdb |
| Descriptor | Cationic trypsin, CALCIUM ION, SULFATE ION, ... (6 entities in total) |
| Functional Keywords | hydrogen bonding, protonation, protein-ligand interaction, hydrolase |
| Biological source | Bos taurus (Bovine) |
| Total number of polymer chains | 1 |
| Total formula weight | 24401.46 |
| Authors | Schiebel, J.,Ngo, K.,Heine, A.,Klebe, G. (deposition date: 2016-12-13, release date: 2018-01-17, Last modification date: 2024-10-16) |
| Primary citation | Schiebel, J.,Gaspari, R.,Wulsdorf, T.,Ngo, K.,Sohn, C.,Schrader, T.E.,Cavalli, A.,Ostermann, A.,Heine, A.,Klebe, G. Intriguing role of water in protein-ligand binding studied by neutron crystallography on trypsin complexes. Nat Commun, 9:3559-3559, 2018 Cited by PubMed Abstract: Hydrogen bonds are key interactions determining protein-ligand binding affinity and therefore fundamental to any biological process. Unfortunately, explicit structural information about hydrogen positions and thus H-bonds in protein-ligand complexes is extremely rare and similarly the important role of water during binding remains poorly understood. Here, we report on neutron structures of trypsin determined at very high resolutions ≤1.5 Å in uncomplexed and inhibited state complemented by X-ray and thermodynamic data and computer simulations. Our structures show the precise geometry of H-bonds between protein and the inhibitors N-amidinopiperidine and benzamidine along with the dynamics of the residual solvation pattern. Prior to binding, the ligand-free binding pocket is occupied by water molecules characterized by a paucity of H-bonds and high mobility resulting in an imperfect hydration of the critical residue Asp189. This phenomenon likely constitutes a key factor fueling ligand binding via water displacement and helps improving our current view on water influencing protein-ligand recognition. PubMed: 30177695DOI: 10.1038/s41467-018-05769-2 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.337 Å) |
Structure validation
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