3WDD

Mutant N-terminal domain of Mycobacterium tuberculosis ClpC1, F2Y, bound to Cyclomarin A

3WDD の概要

• エントリーDOI: 10.2210/pdb3wdd/pdb
• 関連するPDBエントリー: 3WDE 3wdb 3wdc
• 関連するBIRD辞書のPRD_ID: PRD_001124
• 分子名称: Probable ATP-dependent Clp protease ATP-binding subunit, Cyclomarin A, ACETATE ION, ... (4 entities in total)
• 機能のキーワード: chaperone, chaperone-antimicrobial protein complex, chaperone/antimicrobial protein
• 由来する生物種: Mycobacterium tuberculosis; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 18211.93

構造登録者

Vasudevan, D.,Noble, C.G. (登録日: 2013-06-14, 公開日: 2013-09-18, 最終更新日: 2024-10-30)

主引用文献

Vasudevan, D.,Rao, S.P.S.,Noble, C.G.
Structural basis of mycobacterial inhibition by cyclomarin A
J.Biol.Chem., 288:30883-30891, 2013

PubMed Abstract: Cyclomarin A (CymA) was identified as a mycobactericidal compound targeting ClpC1. However, the target was identified based on pulldown experiments and in vitro binding data, without direct functional evidence in mycobacteria. Here we show that CymA specifically binds to the N-terminal domain of ClpC1. In addition we have determined the co-crystal structure of CymA bound to the N-terminal domain of ClpC1 to high resolution. Based on the structure of the complex several mutations were engineered into ClpC1, which showed reduced CymA binding in vitro. The ClpC1 mutants were overexpressed in mycobacteria and two showed resistance to CymA, providing the first direct evidence that ClpC1 is the target of CymA. Phe(80) is important in vitro and in cells for the ClpC1-CymA interaction and this explains why other bacteria are resistant to CymA. A model for how CymA binding to the N-terminal domain of ClpC1 leads to uncontrolled proteolysis by the associated ClpP protease machinery is discussed.

PubMed: 24022489
DOI: 10.1074/jbc.M113.493767

実験手法

X-RAY DIFFRACTION (1.18 Å)