更新于：2024-11-01

STT3A x STT3B

更新于：2024-11-01

基本信息

关联

项与 STT3A x STT3B 相关的药物

STT3A/B Inhibitors(GSK)

靶点

STT3A x STT3B

作用机制

STT3A 抑制剂 [+1]

在研机构

Vir Biotechnology, Inc. [+2]

原研机构

GlaxoSmithKline LLC

在研适应症

病毒感染

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 STT3A x STT3B 相关的临床结果

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100 项与 STT3A x STT3B 相关的转化医学

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0 项与 STT3A x STT3B 相关的专利（医药）

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项与 STT3A x STT3B 相关的文献（医药）

2024-10-01·Heliyon

Targeted metabolomics of muscle amino acid profles and hepatic transcriptomics analyses in grass carp (Ctenopharyngodon idellus) fed with broad beans

Article

作者: Cheng, Wenjie ; Xie, Yuxiao ; Yi, Lanlan ; Zhu, Junhong ; Hao, Meilin ; Zhao, Sumei

While tissue amino acid compositions reflect that of the dietary protein source, and the liver orchestrates amino acid metabolism. In this study, we investigated the muscle amino acid profiles in ordinary and crisp grass carp. The 22 amino acids were measured, and seventeen showed significant concentration differences. To understand the molecular mechanisms behind changes, we analyzed the liver transcriptome, and the 2519 differentially expressed genes (DEGs) were identified, with 1156 up-regulated and 1363 down-regulated genes. DEGs were enriched in ribosome-related biological processes. KEGG pathway analysis showed enrichment in tryptophan metabolism, lysine degradation, valine, leucine and isoleucine degradation, galactose metabolism, and glutathione metabolism with up-regulated genes, arginine and proline metabolism, arginine biosynthesis and alanine, aspartate, amino sugar and nucleotide sugar metabolism, N-Glycan biosynthesis and glutamate metabolism with down-regulated genes. A protein-protein interaction network with 260 nodes and 249 edges was constructed, and 3 modules were extracted. The top 10 hub genes with close connections to other nodes were ITM1, STT3B, SEL1L, UGGT1, MLEC, IL1B, ALG5, KRTCAP2, NFKB2, and IRAK3. In summary, this study identified candidate genes and focused on amino acid and glycan metabolism pathways, providing a reference for further investigation into liver amino acid metabolism in grass carp fed with broad beans.

2024-07-15·The FASEB Journal

Acceptors stability modulates the efficiency of post‐translational protein N‐glycosylation

Article

作者: Caramelo, Julio J ; Labriola, Carlos A ; Couto, Facundo L ; Labanda, María S ; Couto, Paula M ; Guardia, Carlos M A

AbstractN‐glycosylation is the most common protein modification in the eukaryotic secretory pathway. It involves the attachment a high mannose glycan to Asn residues in the context of Asn‐X‐Ser/Thr/Cys, a motif known as N‐glycosylation sequon. This process is mediated by STT3A and STT3B, the catalytic subunits of the oligosaccharyltransferase complexes. STT3A forms part of complexes associated with the SEC61 translocon and functions co‐translationally. Vacant sequons have another opportunity for glycosylation by complexes carrying STT3B. Local sequence information plays an important role in determining N‐glycosylation efficiency, but non‐local factors can also have a significant impact. For instance, certain proteins associated with human genetic diseases exhibit abnormal N‐glycosylation levels despite having wild‐type acceptor sites. Here, we investigated the effect of protein stability on this process. To this end, we generated a family of 40 N‐glycan acceptors based on superfolder GFP, and we measured their efficiency in HEK293 cells and in two derived cell lines lacking STT3B or STT3A. Sequon occupancy was highly dependent on protein stability, improving as the thermodynamic stability of the acceptor proteins decreases. This effect is mainly due to the activity of the STT3B‐based OST complex. These findings can be integrated into a simple kinetic model that distinguishes local information within sequons from global information of the acceptor proteins.

2024-01-01·Biomedicine & Pharmacotherapy

Delta-tocotrienol disrupts PD-L1 glycosylation and reverses PD-L1-mediated immune suppression

Article

作者: Yin, Shutao ; Sun, Zhenou ; Hu, Hongbo ; Fan, Lihong ; Ma, Xuan ; Zhao, Chong

PD-L1-mediated immune escape plays an important role in cancer development and progression. Targeting PD-L1 is consider to be an attractive approach for cancer treatment. PD-L1 is a heavily N-linked glycosylated protein, and the glycosylation of PD-L1 is essential for its ability to interact with its receptor PD-1 to mediate immune suppression. In the present study, we demonstrated for the first time that delta-tocotrienol (δ-T3) not any of the other forms of vitamin E was able to disrupt PD-L1 glycosylation mechanistically associated with the suppression of TCF4-STT3a/STT3b axis. The inhibition of PD-L1 glycosylation by δ-T3 resulted in the decrease of PD-L1 expression and its exosomal secretion, leading to the reduction of PD-L1 and PD-1 interaction, and reversing PD-L1-mediated immune suppression, which in turn contributed to the inhibitory effect on tumor growth. The findings of the present study provide a novel mechanistic interpretation for the superior anticancer activity of δ-T3 among 8 isomers of the vitamin E.