the c-terminal domain of the arabinosyltransferase mycobacterium tuberculosis embc is a lectin-like carbohydrate binding modulearabinosyltransferase结核分枝杆菌的c端域embc lectin-like碳水化合物绑定模块.pdfVIP

The C-Terminal Domain of the Arabinosyltransferase Mycobacterium tuberculosis EmbC Is a Lectin-Like Carbohydrate Binding Module 1 1 1 1 1 Luke J. Alderwick , Georgina S. Lloyd , Hemza Ghadbane , John W. May , Apoorva Bhatt , Lothar 2 ¨ 1 1 Eggeling , Klaus Futterer *, Gurdyal S. Besra * ¨ ¨ ¨ 1 School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom, 2 Institut fur Biotechnologie I, Forschungszentrum Julich, Julich, Germany Abstract The D-arabinan-containing polymers arabinogalactan (AG) and lipoarabinomannan (LAM) are essential components of the unique cell envelope of the pathogen Mycobacterium tuberculosis. Biosynthesis of AG and LAM involves a series of membrane-embedded arabinofuranosyl (Araf) transferases whose structures are largely uncharacterised, despite the fact that several of them are pharmacological targets of ethambutol, a frontline drug in tuberculosis therapy. Herein, we present the crystal structure of the C-terminal hydrophilic domain of the ethambutol-sensitive Araf transferase M. tuberculosis EmbC, which is essential for LAM synthesis. The structure of the C-terminal domain of EmbC (EmbCCT) encompasses two sub- domains of different folds, of which subdomain II shows distinct similarity to lectin-like carbohydrate-binding modules (CBM). Co-crystallisation with a cell wall-derived di-arabinoside acceptor analogue and structural comparison with ligand- bound