Search Results

You searched for all publications:

with publication states 'Published (Approved)'

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

Exact matches
Related results

2 items found (0 items not approved), displaying all items.1

Instruments / Technical Area	Publication Details	Published	Actions
I04-1-Macromolecular Crystallography (fixed wavelength)	Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol Lu Zhang , Yao Zhao , Yan Gao , Lijie Wu , Ruogu Gao , Qi Zhang , Yinan Wang , Chengyao Wu , Fangyu Wu , Sudagar S. Gurcha , Natacha Veerapen , Sarah M. Batt , Wei Zhao , Ling Qin , Xiuna Yang , Manfu Wang , Yan Zhu , Bing Zhang , Lijun Bi , Xian’en Zhang , Haitao Yang , Luke W. Guddat , Wenqing Xu , Quan Wang , Jun Li , Gurdyal S. Besra , Zihe Rao Science 4 DOI: 10.1126/science.aba9102 Show Abstract ▼ Abstract: The arabinosyltransferases EmbA, EmbB, and EmbC are involved in Mycobacterium tuberculosis cell wall synthesis and are recognized as the targets for the anti-tuberculosis drug ethambutol. We have determined cryo-electron microscopy and x-ray crystal structures of mycobacterial EmbA-EmbB and EmbC-EmbC complexes, in the presence of their glycosyl donor and acceptor substrates and with ethambutol. These structures show how the donor and acceptor substrates bind in the active site and how ethambutol inhibits by binding to the same site as both substrates in EmbB and EmbC. The majority of drug-resistant mutations are located nearby to the ethambutol-binding site. Collectively, our work provides a structural basis for understanding the biochemical function and inhibition of arabinosyltransferases and development of new anti-tuberculosis agents.	Apr 2020
I04-1-Macromolecular Crystallography (fixed wavelength)	Crystal structures of membrane transporter MmpL3, an anti-TB drug target Bing Zhang , Jun Li , Xiaolin Yang , Lijie Wu , Jia Zhang , Yang Yang , Yao Zhao , Lu Zhang , Xiuna Yang , Xiaobao Yang , Xi Cheng , Zhijie Liu , Biao Jiang , Hualiang Jiang , Luke W. Guddat , Haitao Yang , Zihe Rao Cell 176, 636 - 648.e13 DOI: 10.1016/j.cell.2019.01.003 Show Abstract ▼ Abstract: Despite intensive efforts to discover highly effective treatments to eradicate tuberculosis (TB), it remains as a major threat to global human health. For this reason, new TB drugs directed toward new targets are highly coveted. MmpLs (Mycobacterial membrane proteins Large), which play crucial roles in transporting lipids, polymers and immunomodulators and which also extrude therapeutic drugs, are among the most important therapeutic drug targets to emerge in recent times. Here, crystal structures of mycobacterial MmpL3 alone and in complex with four TB drug candidates, including SQ109 (in Phase 2b-3 clinical trials), are reported. MmpL3 consists of a periplasmic pore domain and a twelve-helix transmembrane domain. Two Asp-Tyr pairs centrally located in this domain appear to be key facilitators of proton-translocation. SQ109, AU1235, ICA38, and rimonabant bind inside the transmembrane region and disrupt these Asp-Tyr pairs. This structural data will greatly advance the development of MmpL3 inhibitors as new TB drugs.	Jan 2019

Publications Database

Search Results

You searched for all publications:

Search Again...

Subject Areas (check all that apply) select all

Instruments used to collect data (check all that apply) select all

Collaborations involved (check all that apply) select all

Diamond Offline Facilities used

Relevant Technical Areas (check all that apply) select all

Menu for Anonymous User