2N0T

Structural ensemble of the enzyme cyclophilin reveals an orchestrated mode of action at atomic resolution

2N0T の概要

• エントリーDOI: 10.2210/pdb2n0t/pdb
• 関連するPDBエントリー: 2MZU
• 分子名称: Peptidyl-prolyl cis-trans isomerase A (1 entity in total)
• 機能のキーワード: isomerase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cytoplasm : P62937
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 18036.50

構造登録者

Chi, C.N.,Voegeli, B.,Bibow, S.,Strotz, D.,Orts, J.,Guntert, P.,Riek, R. (登録日: 2015-03-13, 公開日: 2015-08-26, 最終更新日: 2024-05-15)

主引用文献

Chi, C.N.,Vogeli, B.,Bibow, S.,Strotz, D.,Orts, J.,Guntert, P.,Riek, R.
A Structural Ensemble for the Enzyme Cyclophilin Reveals an Orchestrated Mode of Action at Atomic Resolution.
Angew.Chem.Int.Ed.Engl., 54:11657-11661, 2015

PubMed Abstract: For enzyme activity, an exact structural and motional orchestration of the active site and its surroundings is believed to be key. In order to reveal such possible phenomena at atomic resolution on the basis of experimental evidence, an experimental restraint driven two-state ensemble of the prototypical enzyme cyclophilin was determined by using a recently introduced exact NOE approach. The ensemble description reveals the presence of an open and a closed state of cyclophilin, which is indicative of large-scale correlated motion. In the open state, the catalytic site is preorganized for catalysis, thus suggesting the mechanism of action to be conformational sampling, while the ligand-binding loop appears to act through an induced fit mechanism. This finding is supported by affinity measurements of a cyclophilin designed to be more open. Overall, more than 60-70 % of the side-chain conformations of cyclophilin appear to be correlated.

PubMed: 26265096
DOI: 10.1002/anie.201503698

実験手法

SOLUTION NMR