The Library
Structural basis of glycerophosphodiester recognition by the mycobacterium tuberculosis substrate-binding protein UgpB
Tools
Tools
Tools
Fenn, Jonathan S., Nepravishta, Ridvan, Guy, Collette S., Harrison, James, Angulo, Jesus, Cameron, Alexander and Fullam, Elizabeth (2019) Structural basis of glycerophosphodiester recognition by the mycobacterium tuberculosis substrate-binding protein UgpB. ACS Chemical Biology, 14 (9). pp. 1879-1887. doi:10.1021/acschembio.9b00204
|
PDF
WRAP-structural-basis-glycerophophodiester-recognition-substrate-binding-Harrison-2019.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (5Mb) | Preview |
Official URL: http://dx.doi.org/10.1021/acschembio.9b00204
Abstract
Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB) and has evolved an incredible ability to survive latently within the human host for decades. The Mtb pathogen encodes for a low number of ATP-binding cassette (ABC) importers for the acquisition of carbohydrates that may reflect the nutrient poor environment within the host macrophages. Mtb UgpB (Rv2833c) is the substrate binding domain of the UgpABCE transporter that recognizes glycerophosphocholine (GPC), indicating that this transporter has a role in recycling glycerophospholipid metabolites. By using a combination of saturation transfer difference (STD) NMR and X-ray crystallography, we report the structural analysis of Mtb UgpB complexed with GPC and have identified that Mtb UgpB not only recognizes GPC but is also promiscuous for a broad range of glycerophosphodiesters. Complementary biochemical analyses and site-directed mutagenesis precisely define the molecular basis and specificity of glycerophosphodiester recognition. Our results provide critical insights into the structural and functional role of the Mtb UgpB transporter and reveal that the specificity of this ABC-transporter is not limited to GPC, therefore optimizing the ability of Mtb to scavenge scarce nutrients and essential glycerophospholipid metabolites via a single transporter during intracellular infection.
| Item Type: | Journal Article | ||||||
|---|---|---|---|---|---|---|---|
| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||||
| Journal or Publication Title: | ACS Chemical Biology | ||||||
| Publisher: | American Chemical Society | ||||||
| ISSN: | 1554-8929 | ||||||
| Official Date: | 21 August 2019 | ||||||
| Dates: |
|
||||||
| Date of first compliant deposit: | 2 September 2019 | ||||||
| Volume: | 14 | ||||||
| Number: | 9 | ||||||
| Page Range: | pp. 1879-1887 | ||||||
| DOI: | 10.1021/acschembio.9b00204 | ||||||
| Status: | Peer Reviewed | ||||||
| Publication Status: | Published | ||||||
| Access rights to Published version: | Open Access | ||||||
| Copyright Holders: | © 2019 American Chemical Society |
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
Downloads
Downloads per month over past year
