4Y11

Trypsin in complex with with BPTI mutant (2S)-2-amino-4,4,4-trifluorobutanoic acid

4Y11 の概要

• エントリーDOI: 10.2210/pdb4y11/pdb
• 関連するPDBエントリー: 4Y0Y 4Y0Z 4Y10
• 分子名称: Cationic trypsin, Pancreatic trypsin inhibitor, SULFATE ION, ... (6 entities in total)
• 機能のキーワード: hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Bos taurus (Cattle); 詳細
• 細胞内の位置: Secreted, extracellular space: P00760; Secreted: P00974
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 30950.58

構造登録者

Loll, B.,Ye, S.,Berger, A.A.,Muelow, U.,Alings, C.,Wahl, M.C.,Koksch, B. (登録日: 2015-02-06, 公開日: 2015-06-24, 最終更新日: 2024-11-20)

主引用文献

Ye, S.,Loll, B.,Berger, A.A.,Mulow, U.,Alings, C.,Wahl, M.C.,Koksch, B.
Fluorine teams up with water to restore inhibitor activity to mutant BPTI.
Chem Sci, 6:5246-5254, 2015

PubMed Abstract: Introducing fluorine into molecules has a wide range of effects on their physicochemical properties, often desirable but in most cases unpredictable. The fluorine atom imparts the C-F bond with low polarizability and high polarity, and significantly affects the behavior of neighboring functional groups, in a covalent or noncovalent manner. Here, we report that fluorine, present in the form of a single fluoroalkyl amino acid side chain in the P1 position of the well-characterized serine-protease inhibitor BPTI, can fully restore inhibitor activity to a mutant that contains the corresponding hydrocarbon side chain at the same site. High resolution crystal structures were obtained for four BPTI variants in complex with bovine β-trypsin, revealing changes in the stoichiometry and dynamics of water molecules in the S1 subsite. These results demonstrate that the introduction of fluorine into a protein environment can result in "chemical complementation" that has a significantly favorable impact on protein-protein interactions.

PubMed: 29449928
DOI: 10.1039/c4sc03227f

実験手法

X-RAY DIFFRACTION (1.3 Å)