PDBsum entry 5mnh

Hydrolase

PDB id: 5mnh

Contents

Protein chain

223 a.a.

Ligands

SO4 ×2

BEN

Metals

_CA

Waters ×198

PDB id:

5mnh

Name:

Hydrolase

Title:

Cationic trypsin in complex with benzamidine (deuterated sample at 295 k)

Structure:

Cationic trypsin. Chain: a. Synonym: beta-trypsin. Ec: 3.4.21.4

Source:

Bos taurus. Cattle. Organism_taxid: 9913

Resolution:

0.93Å R-factor: 0.095 R-free: 0.101

Authors:

J.Schiebel,A.Heine,G.Klebe

Key ref:

J.Schiebel et al. (2018). Intriguing role of water in protein-ligand binding studied by neutron crystallography on trypsin complexes. Nat Commun, 9, 3559. PubMed id: 30177695

Date:

13-Dec-16 Release date: 17-Jan-18

Protein chain

P00760  (TRY1_BOVIN) -  Serine protease 1 from Bos taurus

Seq: 246 a.a.

Struc: 223 a.a.

Enzyme reactions

• Enzyme class: E.C.3.4.21.4 - trypsin.
• Reaction: Preferential cleavage: Arg-|-Xaa, Lys-|-Xaa.

Nat Commun 9:3559 (2018)

PubMed id: 30177695

Intriguing role of water in protein-ligand binding studied by neutron crystallography on trypsin complexes.

J.Schiebel, R.Gaspari, T.Wulsdorf, K.Ngo, C.Sohn, T.E.Schrader, A.Cavalli, A.Ostermann, A.Heine, G.Klebe.

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.