5MNE

Cationic trypsin in its apo form (deuterated sample at 100 K)

Summary for 5MNE

• Entry DOI: 10.2210/pdb5mne/pdb
• Descriptor: Cationic trypsin, CALCIUM ION, SULFATE ION, ... (4 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: 23748.62

Authors

Schiebel, J.,Heine, A.,Klebe, G. (deposition date: 2016-12-13, release date: 2018-01-17, Last modification date: 2024-11-13)

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

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: 30177695
DOI: 10.1038/s41467-018-05769-2

Experimental method

X-RAY DIFFRACTION (1.008 Å)