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Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

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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...
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Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

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Protein Complex Assembly02:41

Protein Complex Assembly

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Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
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Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

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Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
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Complex Numbers01:29

Complex Numbers

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The real number system cannot represent the square root of a negative number, which restricts solutions for certain equations, such as quadratics with negative discriminants. To address this, the complex number system was developed, introducing the imaginary unit i, where i = √(-1). This extension allows for the representation of all roots, including those involving negative radicands.A complex number is written in the form x + yi, where x and y are real numbers. Here, x represents the...
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Formation of Complex Ions03:45

Formation of Complex Ions

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A type of Lewis acid-base chemistry involves the formation of a complex ion (or a coordination complex) comprising a central atom, typically a transition metal cation, surrounded by ions or molecules called ligands. These ligands can be neutral molecules like H2O or NH3, or ions such as CN− or OH−. Often, the ligands act as Lewis bases, donating a pair of electrons to the central atom. These types of Lewis acid-base reactions are examples of a broad subdiscipline called coordination...
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Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases
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Author Spotlight: Developing Tools to Tune the Activity of Tyrosine Phosphatases

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PP1フォスファタゼ複合体: 薬効性がない

Paola Vagnarelli1, Dario R Alessi2

  • 1College of Health and Life Science, Research Institute for Environment Health and Society, Brunel University London, London UB8 3PH, UK.

Cell
|August 25, 2018
PubMed
まとめ

研究者らは,セリン/スレオニンタンパク質フォスファタゼ1 (PP1) のR15B調節サブユニットの新しい阻害剤であるRaphin1を特定した. この発見は 細胞をストレスや神経変性から守る 新しい方法を示しています

科学分野:

  • 生物化学
  • 薬理学について
  • 神経科学

背景:

  • キナーゼ阻害剤は一般的ですが,薬の開発のためのリン酸塩を標的とする研究はあまり行われていません.
  • セリン/スレオニンタンパク質ファスファターゼ1 (PP1) は,その機能を制御する規制サブユニットを持っています.
  • PP1の活動不調は,神経変性疾患を含む様々な疾患に関与しています.

研究 の 目的:

  • PP1 調節サブユニットの新しい阻害剤を特定し,特徴づけること.
  • ニューロプロテクションのためのPP1の規制サブユニットを標的とした治療の可能性を調査する.

主な方法:

  • PP1 調節サブユニットの阻害剤を特定するための化学スクリーニング
  • 抑制剤の選択性と効力を確認するための生化学的測定.
  • ストレスに対する細胞保護を評価するための細胞ベースの測定法.
  • ハンチントン病のマウスモデルを用いた in vivo 研究

主要な成果:

  • PP1 R15Bの選択的阻害剤であるラフィン1の特定
  • Raphin1は,様々なストレスから細胞を保護する効果を示した.

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A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
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Concanavalin A-Based Sedimentation Assay to Measure Substrate Binding of Glucan Phosphatases
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  • ラフィン1治療はハントントン病のマウスモデルで神経変異を遅らせました.
  • 結論:

    • PP1の規制サブユニット,特にR15BとRaphin1をターゲットにすることは,実行可能な薬理学的戦略です.
    • ハンチントン病のような 神経退行性疾患の治療に効く可能性がある.
    • この研究は,薬理学的調節の範囲をキナーゼを超えてフォスファタゼに拡張する.