NSRRC Activity Report 2022

Life Science 049 In summary, this study elucidated the precise binding mode of bacterial STING and the cognate ligand CDG by performing X-ray crystallography. The symmetrical interactions determine the specificity for CDG, which differs from the specificity for CDN of other STING complexes such as 2’3’-cGAMP. The crystal structures further provide a plausible mode of STING oligomerization, which is vital to STING’s biological function. (Reported by Tzu-Ping Ko, Academia Sinica) This report features the work of Yeh Chen and his colleagues published in Nat. Commun. 13 , 26 (2022). TPS 05A Protein Microcrystallography TPS 07A Micro-focus Protein Crystallography TLS 15A1 Biopharmaceuticals Protein Crystallography • X-ray Crystallography, Biological Macromolecules • Protein Structures, Nucleotides, Viral Defense, Life Science References 1. A. Millman, S. Melamed, G. Amitai, R. Sorek, Nat. Microbiol. 5 , 1608 (2020). 2. B. R. Morehouse, A. A. Govande, A. Millman, A. F. A. Keszei, B. Lowey, G. Ofir, S. Shao, R. Sorek, P. J. Kranzusch, Nature 586 , 429 (2020). 3. T.-P. Ko, Y.-C. Wang, C.-S. Yang, M.-H. Hou, C.-J. Chen, Y.-F. Chiu, Y. Chen, Nat. Commun. 13 , 26 (2022). Fig. 2 : Mode of bacterial STING oligomerization. Two orthogonal views of three juxtaposed dimers of Pc STING (a,b) and My STING (c,d) as viewed in crystals with color-differentiated protomers. The unit cells are depicted as cages. A diagram for the extended packing of the Pc STING crystal is depicted in (e) with color-differentiated translucent protein dimers. The bound CDG molecules are indicated in blue. [Reproduced from Ref. 3] (a) (b) (c) (d) (e) Structural Analysis and Engineering of Aldo-Keto Reductase from Glyphosate-Resistant Echinochloa colona Glyphosate is the most widely used non-selective herbicide because of its high efficacy and low cost. Our study revealed the mechanism of aldo-keto reductase mediated glyphosate degradation and engineered a variant, which exhibited a 70% in glyphosate degradation. S ince it was first registered for use as a pesticide in 1974, glyphosate has become the most commonly used organophosphate herbicide. It acts as a 5-enolpyruvylshikimate-3-phosphate synthase inhibitor to block the shikimate pathway and aromatic amino acid biosynthesis. 1 In most plants, glyphosate can be degraded to weakly phytotoxic aminomethyl phosphonic acid and glyoxylate; 2 the underlying mechanisms of this process remain poorly understood. In 2020, a glyphosate-resistant Echinochloa colona ( E. colona ) population from western Australia has been reported. 3 The elevated glyphosate degradation in E. colona is caused by the upregulation of two homologous aldo–keto reductases (AKRs), namely AKR4C16 and AKR4C17. 3 AKR4C16 and AKR4C17 are the first naturally-occurring glyphosate-degrading machinery reported in plants. To explore the mechanism of AKR-mediated glyphosate- degradation, a research team led by Rey-Ting Guo (Hubei University, China) solved the apo-form and cofactor/ glyphosate-bound structures of AKR4C17 from the glyphosate-resistant E. colona . 4 The X-ray diffraction data were collected at TLS 15A1 and TPS 05A of the NSRRC. AKR4C17 displays a triose-phosphate isomerase barrel