3PWB

Bovine trypsin variant X(tripleGlu217Ile227) in complex with small molecule inhibitor

3PWB の概要

• エントリーDOI: 10.2210/pdb3pwb/pdb
• 関連するPDBエントリー: 1V2K 3PWC
• 分子名称: Cationic trypsin, CALCIUM ION, BENZAMIDINE, ... (6 entities in total)
• 機能のキーワード: trypsin-like serine protease, hydrolase, protein binding, duodenum
• 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: 23766.78

構造登録者

Tziridis, A.,Neumann, P.,Kolenko, P.,Stubbs, M.T. (登録日: 2010-12-08, 公開日: 2011-12-21, 最終更新日: 2023-09-13)

主引用文献

Tziridis, A.,Rauh, D.,Neumann, P.,Kolenko, P.,Menzel, A.,Brauer, U.,Ursel, C.,Steinmetzer, P.,Sturzebecher, J.,Schweinitz, A.,Steinmetzer, T.,Stubbs, M.T.
Correlating structure and ligand affinity in drug discovery: a cautionary tale involving second shell residues.
Biol.Chem., 395:891-903, 2014

PubMed Abstract: A high-resolution crystallographic structure determination of a protein-ligand complex is generally accepted as the 'gold standard' for structure-based drug design, yet the relationship between structure and affinity is neither obvious nor straightforward. Here we analyze the interactions of a series of serine proteinase inhibitors with trypsin variants onto which the ligand-binding site of factor Xa has been grafted. Despite conservative mutations of only two residues not immediately in contact with ligands (second shell residues), significant differences in the affinity profiles of the variants are observed. Structural analyses demonstrate that these are due to multiple effects, including differences in the structure of the binding site, differences in target flexibility and differences in inhibitor binding modes. The data presented here highlight the myriad competing microscopic processes that contribute to protein-ligand interactions and emphasize the difficulties in predicting affinity from structure.

PubMed: 25003390
DOI: 10.1515/hsz-2014-0158

実験手法

X-RAY DIFFRACTION (1.63 Å)