PDBsum entry 5mnc

Hydrolase

PDB id: 5mnc

Contents

Protein chain

223 a.a.

Ligands

SO4 ×5

ANL

Metals

_CA

Waters ×378

PDB id:

5mnc

Name:

Hydrolase

Title:

Cationic trypsin in complex with aniline (deuterated sample at 100 k)

Structure:

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

Source:

Bos taurus. Bovine. Organism_taxid: 9913

Resolution:

0.92Å R-factor: 0.108 R-free: 0.122

Authors:

J.Schiebel,A.Heine,G.Klebe

Key ref:

J.Schiebel et al. (2017). Charges Shift Protonation: Neutron Diffraction Reveals that Aniline and 2-Aminopyridine Become Protonated Upon Binding to Trypsin. Angew Chem Int Ed Engl, 56, 4887-4890. PubMed id: 28371253 DOI: 10.1002/anie.201701038

Date:

13-Dec-16 Release date: 24-May-17

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.

DOI no: 10.1002/anie.201701038

Angew Chem Int Ed Engl 56:4887-4890 (2017)

PubMed id: 28371253

Charges Shift Protonation: Neutron Diffraction Reveals that Aniline and 2-Aminopyridine Become Protonated Upon Binding to Trypsin.

J.Schiebel, R.Gaspari, A.Sandner, K.Ngo, H.D.Gerber, A.Cavalli, A.Ostermann, A.Heine, G.Klebe.

ABSTRACT

Hydrogen atoms play a key role in protein-ligand recognition. They determine the quality of established H-bonding networks and define the protonation of bound ligands. Structural visualization of H atoms by X-ray crystallography is rarely possible. We used neutron diffraction to determine the positions of the hydrogen atoms in the ligands aniline and 2-aminopyridine bound to the archetypical serine protease trypsin. The resulting structures show the best resolution so far achieved for proteins larger than 100 residues and allow an accurate description of the protonation states and interactions with nearby water molecules. Despite its low pK_aof 4.6 and a large distance of 3.6 Å to the charged Asp189 at the bottom of the S1 pocket, the amino group of aniline becomes protonated, whereas in 2-aminopyridine, the pyridine nitrogen picks up the proton although its amino group is 1.6 Å closer to Asp189. Therefore, apart from charge-charge distances, tautomer stability is decisive for the resulting binding poses, an aspect that is pivotal for predicting correct binding.