タンパク質工学によるイオンペア逆転が成功する可能性が低いのはなぜか
1Department of Chemistry, University of Southern California, Los Angeles 90089-0482.
Nature
|July 21, 1988
まとめ
タンパク質イオンペアの極性を逆転させるのは難しい. マイクロ環境とは
科学分野:
- タンパク質エンジニアリングは,
- バイオケミストリー バイオケミストリー
- 計算生物学とは,計算生物学である.
背景:
- 遺伝子工学はタンパク質の構造・機能の研究を可能にしますが,効果的なタンパク質設計には欠けています.
- タンパク質におけるイオン対の極性を逆転させることは,理論的にシンプルだが,実験的に難しい設計戦略である.
- 以前の実験は,極性の逆転が予想ほど成功していないことを示唆している.
研究 の 目的:
- タンパク質の活性部位におけるイオン対の極性を逆転させるエネルギーの可行性を調査する.
- 特定のイオンペア配列に最適化された酵素が逆極性に対して効果が低い理由を説明するために.
主な方法:
- タンパク質の活性部位内のイオンペアの半量的なエネルギー計算.
- タンパク質の微環境とその有効介電常数の役割の分析.
主要な成果:
- ネガティブ・ポジティブ (-) イオンペアに最適化された酵素は,ポジティブ・ネガティブ (+-) イオンペアに対して効果が低い.
- 微環境の低効果介電定数 (ε ≈ 13) は,ネイティブイオンペアを安定させる.
- 逆離子対の配列は,著しく異なる介電定数 (ε ≈ 80) を経験し,不安定化につながります.
結論:
- 電子環境の介電特性には,イオンペアの安定性と酵素活性部位における機能が不可欠である.
- 機能的なイオンペアの直接の極性逆転は,異なる介電環境のためにエネルギー的に不利です.
- これらのエネルギー要因を理解することは,タンパク質の設計と工学を進めるために極めて重要です.
さらに関連する動画
09:16In Vitro Directed Evolution of a Restriction Endonuclease with More Stringent Specificity
Published on: March 25, 2020
10:31Residue-Specific Exchange of Proline by Proline Analogs in Fluorescent Proteins: How "Molecular Surgery" of the Backbone Affects Folding and Stability
Published on: February 3, 2022
関連する概念動画
Conservation of Protein Domains Over Different Proteins
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to form...
Ligand Binding Sites
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-protein Interfaces
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...
Ion Exchange
Ion exchange chromatography separates charged molecules from a solution by reversibly exchanging them with mobile, or 'active', ions associated with the oppositely charged stationary phase. This method can be used to separate ions, soften and deionize water, and purify solutions. The polymers comprising the ion-exchange column are high-molecular-weight and chemically stable polymers, crosslinked to be porous and essentially insoluble. They are also functionalized with either acidic or basic...
Ionic Association
The ionic association is the association of oppositely charged ions in an electrolyte solution to form ion pairs. Bjerrum defined ion pairs as two oppositely charged ions whose electrostatic attraction exceeds the thermal energy of the system, typically expressed as 2kT. Electrostatic attraction depends on ionic charge, separation distance, and the dielectric constant of the medium. Thermal energy, represented by kT, reflects the tendency of ions to move independently due to molecular motion.
Pore Transport and Ion-Pair Transport
Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct microscopic...
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct microscopic...
