相关实验视频

Updated: Jul 5, 2025

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Published on: December 14, 2017

确定人与老鼠之间酸化BACE1在中与其酸化的GSK3β在Thr252在体外之间的结构变化

Jazziel Velazquez Toledano^1,2, Martiniano Bello², José Correa Basurto²

¹Laboratorio de Biofísica y Biocatálisis, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Ciudad de México 11340, México.

ACS chemical neuroscience

|January 16, 2024

概括

阿尔茨海默氏病涉及β位粉样前体蛋白分裂酶1 (BACE1) 的酸化. 这项研究揭示了BACE1酸化如何影响其结构和药物相互作用,为未来的阿尔茨海默病抑制剂设计提供了见解.

科学领域:

神经科学是一个神经科学.
生物化学生物化学
计算生物学计算生物学

背景情况:

阿尔茨海默氏病 (AD) 的发病包括粉样β1-42 (Aβ_1-42) 的产生,由β位粉样前体蛋白分裂酶1 (BACE1) 调节.
酸化,特别是Thr252,增强了BACE1的酶活性,这表明它在疾病进展中发挥了作用.

研究的目的:

研究BACE1酸化对其结构,基质结合和抑制剂亲和力的影响.
用计算和体外方法探索人类和老鼠BACE1的潜在酸化部位.

主要方法:

在使用酸化预测剂和分子动力学模拟的分析中.
对接研究和MMGBSA计算以评估约束亲和关系.
在体外酸化试验中使用GSK3β.

主要成果:

在BACE1上确定了多个潜在的酸化部位,包括Thr252,Ser71和Ser127 (大鼠).
酸化显著改变BACE1的构造和与粉样蛋白前体蛋白 (APP) 和抑制剂的结合亲和力.
在Ser71中酸化的老鼠BACE1与APP具有最佳的结合,而抑制剂对酸化的老鼠BACE1具有较高的亲和力,相比于人类BACE1.

结论:

BACE1酸化是其构造和连接体识别的关键调节者.
了解酸化模式对于设计用于阿尔茨海默病治疗的有效BACE1抑制剂至关重要.
观察到的抑制剂亲和力的差异可能解释临床试验的失败.

关键词:

这就是为什么APP APP APP APP.在BACE1中获得了BACE1学位.糖原合成酶激酶3酶3是什么意思在学研究中.酸化的方法是:光化.

更多相关视频

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes

Author Spotlight: Evaluating Biophysical Assays for Characterizing PROTACS Ternary Complexes

Published on: January 12, 2024

Oligopeptide Competition Assay for Phosphorylation Site Determination

Oligopeptide Competition Assay for Phosphorylation Site Determination

Published on: May 18, 2017

相关概念视频

Protein Kinases and Phosphatases

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...

Amplifying Signals via Enzymatic Cascade

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...

PI3K/mTOR/AKT Signaling Pathway

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...