| 1 | Glutathione disrupts galectin-10 Charcot-Leyden crystal formation to possibly ameliorate eosinophil-based diseases such as asthma显示文摘Charcot-Leyden crystals(CLCs)are the hallmark of many eosinophilic-based diseases,such as asthma.Here,we report that reduced glutathione(GSH)disrupts CLCs and inhibits crystallization of human galectin-10(Gal-10).GSH has no effect on CLCs from monkeys(Macaca fascicularis or M.mulatta),even though monkey Gal-10s contain Cys29 and Cys32.Interestingly,human Gal-10 contains another cysteine residue(Cys57).Because GSH cannot disrupt CLCs formed by the human Gal-10 variant C57A or inhibit its crystallization,the effects of GSH on human Gal-10 or CLCs most likely occur by chemical modification of Cys57.We further report the crystal structures of Gal-10 from M.fascicularis and M.mulatta,along with their ability to bind to lactose and inhibit erythrocyte agglutination.Structural comparison with human Gal-10 shows that Cys57 and Gln75 within the ligand binding site are responsible for the loss of lactose binding.Pull-down experiments and mass spectrometry show that human Gal-10 interacts with tubulinα-1B,with GSH,GTP and Mg^(2+)stabilizing this interaction and colchicine inhibiting it.Overall,this study enhances our understanding of Gal-10 function and CLC formation and suggests that GSH may be used as a pharmaceutical agent to ameliorate CLC-induced diseases. | Heya Na Hend Sayed Gabriela Jaramillo Ayala Xing Wang Yuhan Liu Jinyi Yu Tianhao Liu Kevin H.Mayo Jiyong Su | 2023 | Acta Biochimica et Biophysica Sinica2023，55，4： | 0 |
| 2 | Structural basis for glucosylsucrose synthesis by a member of theα-1,2-glucosyltransferase family显示文摘Glucosylsucroses are potentially useful as additives in cosmetic and pharmaceutical formulations.Although enzymatic synthesis of glucosylsucroses is the most efficient method for their production,the key enzyme that produces them has remained unknown.Here,we report that glucosylsucrose synthase from Thermosynechococcus elongatus(TeGSS)catalyzes the synthesis of glucosylsucrose using sucrose and UDP-glucose as substrates.These saccharides are homologous to glucosylsucroses produced by Nostoc sp.PCC 7120(referred to as protein alr1000).When the ratio of UDP-glucose to sucrose is relatively high,TeGSS from cyanobacteria can hydrolyze excess UDP-glucose to UDP and glucose,indicating that sucrose provides a feedback mechanism for the control of glucosylsucrose synthesis.In the present study,we solved the crystal structure of TeGSS bound to UDP and sucrose.Our structure shows that the catalytic site contains a circular region that may allow glucosylsucroses with a right-hand helical structure to enter the catalytic site.Because active site residues Tyr18 and Arg179 are proximal to UDP and sucrose,we mutate these residues(i.e.,Y18F and R179A)and show that they exhibit very low activity,supporting their role as catalytic groups.Overall,our study provides insight into the catalytic mechanism of TeGSS. | Qiuyu Han Yuan Yao Yuhan Liu Wenlu Zhang Jinyi Yu Heya Na Tianhao Liu Kevin HMayo Jiyong Su | 2022 | Acta Biochimica et Biophysica Sinica2022，54，4： | 0 |
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