相关实验视频

Updated: Jul 13, 2025

Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology

Screening Traditional Chinese Medicine Compounds for Inhibiting UCHL3 Activity Based on Molecular Docking and Deubiquitinating Enzyme Probe Technology

Published on: November 22, 2024

一种氨酸-8-ol UGGT 的亚毫米度抑制剂,ER 糖蛋白折叠质量控制检查点

Kevin P Guay¹, Roberta Ibba^2,3, J L Kiappes²

¹Department of Biochemistry and Molecular Biology, and Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA, USA.

|October 12, 2023

概括

研究人员发现了一种新的小分子,5-[(morpholin-4-yl) methyl]quinolin-8-ol (5M-8OH-Q),它与UDP-葡萄糖糖蛋白葡萄糖转移酶 (UGGT) 酶结合. 这一发现为开发针对各种疾病的新疗法铺平了道路.

科学领域:

生物化学和分子生物学
酶学是一种酶学.
药物发现药物发现药物发现

背景情况:

UDP-葡萄糖糖蛋白葡萄糖转移酶 (UGGT) 对于内细胞网膜 (ER) 糖蛋白折叠质量控制至关重要.
UGGT调制对病毒感染,罕见遗传疾病和癌症具有治疗潜力.
目前缺乏选择性UGGT抑制剂.

研究的目的:

确定和描述UDP-葡萄糖糖蛋白葡萄糖转移酶 (UGGT) 的新型选择性抑制剂.
探索用于治疗应用的小分子向保存的UGGT动机的潜力.

主要方法:

在GT24上选小分子与保留的表面图案结合.
用联体增强的光测试来确定结合亲和力 (*in vitro*).
细胞测试以评估人类UGGT异型的抑制 (*在细胞*).
竞争实验,以评估与甘氨酸基质的结合独家性.

主要成果:

小分子5-[(morpholin-4-yl) methyl]quinolin-8-ol (5M-8OH-Q) 与47μM亲和度的*Ct*UGGT_GT24的保留的"WY"表面图案结合在一起.
在750μM以上的度下,5M-8OH-Q显示出对人类UGGT异型的抑制活性.
5M-8OH-Q与*Ct*UGGT_GT24的结合与M5-9糖结合是相互排斥的.

结论:

5M-8OH-Q代表了一种用于开发选择性UGGT抑制剂的新型化学支架.
鉴定的结合部位是UGGT特异性的,为向治疗开发提供了潜在的潜力.
基于5M-8OH-Q的进一步药物化学努力预计将产生下一代UGGT抑制剂.

关键词:

细胞生物学细胞生物学化学化学化学细胞生物学的功能方面.

更多相关视频

Uracil-DNA Glycosylase Assay by Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry Analysis

Uracil-DNA Glycosylase Assay by Matrix-assisted Laser Desorption/Ionization Time-of-flight Mass Spectrometry Analysis

Published on: April 22, 2022

4D Imaging of Protein Aggregation in Live Cells

4D Imaging of Protein Aggregation in Live Cells

Published on: April 5, 2013

相关概念视频

Protein Folding Quality Check in the RER

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...