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Updated: May 12, 2026
09:16
Oligopeptide Competition Assay for Phosphorylation Site Determination
Published on: May 18, 2017
アロステルリン酸ファスファターゼ阻害剤の選択的検出
Ralf Schneider1, Claudia Beumer, Jeffrey R Simard
1Chemical Genomics Centre der Max-Planck-Gesellschaft, Dortmund, Germany.
Journal of the American Chemical Society
|April 25, 2013
まとめ
新種のフォスファターゼ阻害剤の開発は,がんなどの疾患の治療に不可欠です. この研究は,前回の方法の限界を克服し,アロステルリン酸塩酵素阻害剤を発見するための新しい高通量スクリーニングアッセイを導入しています.
科学分野:
- バイオケミストリー バイオケミストリー
- 酵素学 酵素学とは
- ドラッグ・ディスカバリー・ドリッグ・ディスカバリー・ドリッグ・ディスカバリー・ドリッグ・ディスカバリー
背景:
- キナーゼとフォスファタゼによるタンパク質のリン酸化は,細胞機能を調節する.
- リン酸化の調節不良は,がんや炎症などの病気に寄与する.
- キナーゼ阻害剤は成功していますが,選択性やチャージに関する問題により,ホスファターゼ阻害剤は臨床的に承認されていません.
研究 の 目的:
- アロステリック・フォスファターゼ阻害剤の発見のための新しい測定法を開発する.
- アロステル調節器の適切なスクリーニングシステムの欠如を解決する.
- 改善された薬理学的特性を有する薬剤候補の特定を可能にする.
主な方法:
- 新しい結合測定法の開発.
- アロステリックポケットに結合するリガンドを検出するために設計されたアッセイ.
- 高通量スクリーニング (HTS) のために検証されたアッセイ.
主要な成果:
- このアッセイは,タンパク質チロシンフォスファタゼ1B (PTP1B) のアロステリックポケットに結合するリガンドを成功裏に検出します.
- この測定は,アロステリックリンガンドと基板競争性リンガンドの明確な差別を示しています.
- このアッセイは,高通量スクリーニングアプリケーションに適しています.
結論:
- アロステルリン酸塩酵素阻害剤の発見のための新しい,選択的測定法が開発されました.
- このアッセイにより,新しいフォスファタゼ調節剤の特定が容易になります.
- このアッセイは,以前の方法の限界を克服し,新しい治療法への道を開く.
関連する概念動画
01:08Allosteric Regulation
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
02:54Protein 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...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
01:19Allosteric Proteins-ATCase
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis pathway,...
01:30Enzyme Inhibition
Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
01:27Transducer Mechanism: Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include: