Cryo-EM snapshots of mycobacterial arabinosyltransferase complex EmbB2-AcpM2
Research output: Contribution to journal › Article › peer-review
Colleges, School and Institutes
- Nankai University
- University of Chinese Academy of Sciences
- Max Planck Institute for Biophysics
- ShanghaiTech University
- Tsinghua University
- School of Biosciences, University of Birmingham, Birmingham, UK; Birmingham Institute for Forest Research, University of Birmingham, Birmingham, UK.
- The University of Queensland
Inhibition of Mycobacterium tuberculosis (Mtb) cell wall assembly is an established strategy for anti-TB chemotherapy. Arabinosyltransferase EmbB, which catalyzes the transfer of arabinose from the donor decaprenyl-phosphate-arabinose (DPA) to its arabinosyl acceptor is an essential enzyme for Mtb cell wall synthesis. Analysis of drug resistance mutations suggests that EmbB is the main target of the front-line anti-TB drug, ethambutol. Herein, we report the cryo-EM structures of Mycobacterium smegmatis EmbB in its "resting state" and DPA-bound "active state". EmbB is a fifteen-transmembrane-spanning protein, assembled as a dimer. Each protomer has an associated acyl-carrier-protein (AcpM) on their cytoplasmic surface. Conformational changes upon DPA binding indicate an asymmetric movement within the EmbB dimer during catalysis. Functional studies have identified critical residues in substrate recognition and catalysis, and demonstrated that ethambutol inhibits transferase activity of EmbB by competing with DPA. The structures represent the first step directed towards a rational approach for anti-TB drug discovery.
|Number of pages||13|
|Journal||Protein & cell|
|Early online date||3 May 2020|
|Publication status||Published - Jul 2020|