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関連する概念動画

Affinity and Avidity01:41

Affinity and Avidity

38.7K
Overview
38.7K
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

14.9K
The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
14.9K
Electron Affinity03:07

Electron Affinity

43.1K
The electron affinity (EA) is the energy change for adding an electron to a gaseous atom to form an anion (negative ion).
43.1K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

7.4K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
7.4K
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

877
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
877
Adrenergic Agonists: Therapeutic Uses01:30

Adrenergic Agonists: Therapeutic Uses

1.8K
Adrenergic agonists have diverse therapeutic uses across various medical conditions and emergencies.
Emergency and Intensive Care Unit (ICU) applications: Pressor agents increase blood pressure, heart rate, and contractility in shock and organ failure situations. Dopamine can induce vasodilation and stimulate adrenoceptors. Endogenous catecholamines are effective in treating cardiogenic shock. α2-agonists like clonidine can reverse anesthesia-induced hypertension.
Allergies and...
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関連する実験動画

Updated: Jan 25, 2026

Determining Binding Affinity KD of Radiolabeled Antibodies to Immobilized Antigens
07:39

Determining Binding Affinity KD of Radiolabeled Antibodies to Immobilized Antigens

Published on: June 23, 2022

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GPCRにおける高親和性アゴニスト結合の分子基礎

Tony Warne1, Patricia C Edwards1, Andrew S Doré2

  • 1Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.

Science (New York, N.Y.)
|May 11, 2019
PubMed
まとめ

Gタンパク質結合受容体 (GPCRs) は,その活性状態において,より高いアゴニスト親和性を示す. 構造分析はより小さな結合部位と 原子接触の増加を明らかにし,この強化された親和性を説明します.

さらに関連する動画

Protein Purification-free Method of Binding Affinity Determination by Microscale Thermophoresis
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Protein Purification-free Method of Binding Affinity Determination by Microscale Thermophoresis

Published on: August 15, 2013

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Comparing the Affinity of GTPase-binding Proteins using Competition Assays
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Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Published on: October 8, 2015

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関連する実験動画

Last Updated: Jan 25, 2026

Determining Binding Affinity KD of Radiolabeled Antibodies to Immobilized Antigens
07:39

Determining Binding Affinity KD of Radiolabeled Antibodies to Immobilized Antigens

Published on: June 23, 2022

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Protein Purification-free Method of Binding Affinity Determination by Microscale Thermophoresis
10:22

Protein Purification-free Method of Binding Affinity Determination by Microscale Thermophoresis

Published on: August 15, 2013

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Comparing the Affinity of GTPase-binding Proteins using Competition Assays
10:37

Comparing the Affinity of GTPase-binding Proteins using Competition Assays

Published on: October 8, 2015

9.6K

科学分野:

  • 生物化学
  • 構造生物学
  • 薬理学について

背景:

  • Gタンパク質結合受容体 (GPCRs) は,細胞表面受容体として重要である.
  • GPCRは,非活性状態と比較して,活性状態でアゴニストに対するより高い親和性を示します.
  • この親和差の基礎にある分子メカニズムは,まだ完全に理解されていません.

研究 の 目的:

  • GPCRsの活性状態におけるアゴニスト afinityの増加の構造的基礎を解明する.
  • アゴニストに結合するβ1アドレノ受容体 (β1AR) の活性状態と非活性状態を比較する.

主な方法:

  • 形状特異なナノボディと異なる有効性のアゴニストを複合したβ1ARの4つの活性状態構造を決定した.
  • これらの活性状態の構造を,同じリガンドに結合するβ1ARの以前に決定された非活性状態の構造と比較した.

主要な成果:

  • アクティブ状態と非アクティブ状態の間で,オーソステル結合部位の有意な減少 (24 - 42%) が観察されました.
  • 受容体とリガンドの間の潜在的な水素結合は,活性状態では短く見られた.
  • β1ARとリガンドの間の原子接触の増加 (最大30%) が活性型で観察された.

結論:

  • β1ARの活性状態のより小さく,より制限された結合ポケットは,原子接触の増加とより短い水素結合につながります.
  • これらの構造的変化は,活性GPCRで観察されたアゴニストの強固な親和性に対する分子説明を提供する.
  • この結果は,GPCRに結合する構造的に多様なアゴニストの幅広い範囲に適用できます.