5MNC

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

5MNC の概要

• エントリーDOI: 10.2210/pdb5mnc/pdb
• 分子名称: Cationic trypsin, CALCIUM ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: hydrogen bonding, protonation, protein-ligand interaction, hydrolase
• 由来する生物種: Bos taurus (Bovine)
• 細胞内の位置: Secreted, extracellular space: P00760
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23937.81

構造登録者

Schiebel, J.,Heine, A.,Klebe, G. (登録日: 2016-12-13, 公開日: 2017-05-24, 最終更新日: 2024-11-13)

主引用文献

Schiebel, J.,Gaspari, R.,Sandner, A.,Ngo, K.,Gerber, H.D.,Cavalli, A.,Ostermann, A.,Heine, A.,Klebe, G.
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, 2017

PubMed 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 of 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.

PubMed: 28371253
DOI: 10.1002/anie.201701038

実験手法

X-RAY DIFFRACTION (0.916 Å)