At 2 PM on April 23 (EDT), the international top academic journal Science published the latest results of a joint research team from Shanghai Tech University, Nankai University and University of Birmingham in their online edition. The researchers successfully analyzed the high-resolution three-dimensional structure of the anti-tuberculosis first-line drug ethambutol target protein and drug complex, first elucidated the mechanism of inhibition of this first-line drug that has been used to cure countless tuberculosis infections for nearly 60 years, and for the first time revealed the molecular mechanism of clinical Mycobacterium tuberculosis resistance to ethambutol.

Figure 1: (A, B) Binding mode of ethambutol (C, D, E) Structural superposition found that ethambutol occupied the binding site of the substrate arabinose (D-site and A0-site)

Figure 2: (A) Schematic representation of the enzyme reaction catalyzed by the EmbA-EmbB-AcpM2 complex, which transfers an arabinose residue from DPA in an α(1→3)-linkage to an arabinan acceptor e.g. NV1. (B) Schematic representation of the α(1→5) arabinosyltransferase reaction catalyzed by EmbC2-AcpM2 complex, (C) Topological structure of EMB protein

The research was published online in an article entitled “Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol” in Science. Prof. Zihe Rao (Nankai University’s State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, College of Pharmacology), Prof. Quan Wang (Shanghai Tech University, also 2014 doctoral graduate of Nankai University), and Prof. Gurdyal Besra (University of Birmingham), Dr. Jun Li (ShanghaiTech University) are co-credited authors. Dr. Lu Zhang (2019 doctoral graduate of Nankai University’s College of Life Sciences) and Dr. Yao Zhao (doctoral student of Shanghai Tech University) are co-first authors. Prof. Wei Zhao (Nankai University’s College of Pharmacology) is one of the cooperating researchers involved. Fangyu Wu, 2016 undergraduate of Nankai University’s College of Life Sciences, participated in the publishing of the paper. Nankai University’s Frontiers Science Center for Cell Response is one of the corresponding units.

It is worth mentioning that Fangyu Wu, 2016 undergraduate of Nankai University’s College of Life Sciences, participated in the publishing of the paper. In May 2019, Fangyu Wu joined  Prof. Zihe Rao’s team to start designing the undergraduate project. In September, he was selected for the first year of “the Continuous Cultivating Project from Undergraduate to Postgraduate” of the College, becoming a bachelor-straight-to-doctorate student of Prof. Rao. Nankai University’s College of Life Sciences. “The Continuous Cultivating Project from Undergraduate to PhD” has been implemented in order to fully develop talent cultivation and improve the quality of education for top innovative talents. Third-year undergraduates can submit their application of their own accord. After approval, selection and recommendation by experts, they may obtain the qualification of becoming a bachelor-straight-to-doctorate student and start the course study and scientific research required for master programs in advance. In January 2020, as a test unit of “the Undergraduate-Master-PhD Continuous Cultivation Program” as regulated by the Ministry of Education, Nankai University launched the project in many colleges and schools based on early implementation, striving to establish a new mode of excellent talent cultivation with Nankai’s characteristics.

Link to the paper:

https://science.sciencemag.org/content/early/2020/04/22/science.aba9102

(Reported by Junhui Wu, Translated by Yuchen Shi, Edited by Daniel Stefan and JianjingYun)