強化された水嫌性を示す基本的なアミノ酸の設計と応用
Juliana K Kretsinger1, Joel P Schneider
1Department of Chemistry and Biochemistry, University of Delaware, Newark, DE 19716-2522, USA.
Journal of the American Chemical Society
|June 26, 2003
まとめ
メチル基を持つ新しい非コーディングアミノ酸は,タンパク質の安定性と折り畳みを強化する. モノメチルダイアミノプロピオニン酸 (MMDAP) はタンパク質ヘテロダイマーを安定させ,トリメチルダイアミノプロピオニン酸 (TMDAP) はそれらを不安定化します. ディメチルダイアミノプロピオニン酸 (dmdap) は意外と安定したホモトリマーを形成する.
科学分野:
- タンパク質の設計と工学
- バイオケミストリー バイオケミストリー
- 構造生物学 構造生物学とは
背景:
- タンパク質の設計には,タンパク質の構造と機能を制御するために新しいアミノ酸残留物が必要です.
- ダイアミノプロピオニン酸 (dap) は,化学的に改変できる基本的なアミノ酸です.
- 変化がタンパク質の折り畳みにどのように影響するかを理解することは,タンパク質工学にとって極めて重要です.
研究 の 目的:
- 新規のノンコーディングアミノ酸:モノ-,ディ-,トリメチルジアミノプロピオン酸 (mmdap,dmdap,tmdap) を合成し,特徴づけること.
- タンパク質設計におけるこれらの改変された残留物の有用性を評価し,特に内部の塩橋形成を促進するために.
- これらの残留物がGCN4-p1コイル・コイル・システムの安定性および折り畳みの好みに与える影響を評価する.
主な方法:
- mmdap,dmdap,およびtmdapの残留物の合成.
- これらの残基をGCN4-p1ペプチドに位置16で組み込む.
- 改変されたGCN4-p1ペプチドとアスパルティック酸を含むペプチドの間の異体化の研究.
- ペプチドのホモトリマイゼーションと熱展開の分析.
主要な成果:
- Mmdapを含むヘテロジメは,Dap由来ヘテロジメと比較して0.5kcal/molの安定性の増加を示しました.
- Tmdapを含むヘテロダイマーは安定性が著しく低下し,ステリック障害を示した.
- Dmdapは意外にペプチドのホモトリメリゼーションを誘導し,安定したトリマー (ΔG = 11.8 kcal / mol) を形成しました.
結論:
- メチル化されたダイアミノプロピオニン酸の誘導体は,タンパク質の設計のために調節可能な特性を提供します.
- アミノ酸のサイズと水性抵抗性の小さな変化は,タンパク質の折り畳み方を大きく変えることができます.
- これらの新しい残留物は,タンパク質化学者がタンパク質の構造と安定性を設計するための新しいツールを提供します.
関連する概念動画
Dehydration Synthesis
Dehydration synthesis (also called a condensation reaction) is the chemical process in which two molecules covalently link together to form a new molecule, along with the release of a water molecule. Many physiologically important compounds form by dehydration synthesis reactions, such as complex carbohydrates, proteins, DNA, and RNA.Synthesis of carbohydratesSugar molecules are covalently linked together by dehydration synthesis. During the reaction, the hydroxyl (-OH) group from one reactant...
Amino acids
Amino acids are the monomers that comprise proteins. Each amino acid has the same fundamental structure, which consists of a central carbon atom, or the alpha (α) carbon, bonded to an amino group (NH2), a carboxyl group (COOH), and to a hydrogen atom. Every amino acid also has another atom or group of atoms bonded to the central atom known as the R group. There are 20 common amino acids present in proteins, each with a different R group. Variation in the amino acid sequence is responsible for...
Basicity of Heterocyclic Aromatic Amines
Heterocyclic amines, where the N atom is a part of an alicyclic system, are similar in basicity to alkylamines. Interestingly, the heterocyclic amine having a nitrogen atom as part of an aromatic ring has much less basicity than its corresponding alicyclic counterpart. For this reason, as presented in Figure 1, piperidine (pKb = 2.8) is significantly more basic than pyridine (pKb = 8.8).
Surface Membrane Barriers
The skin and mucous membranes serve as the primary line of defense against pathogens by providing both physical and chemical protection. These barriers are essential in preventing the entry and establishment of microbes, thereby maintaining the integrity of the host.
The outer layer of the skin, the epidermis, is a robust barrier comprising layers of closely packed keratinized cells. This dense arrangement prevents microbes from penetrating the body. The periodic shedding of epidermal cells...
The outer layer of the skin, the epidermis, is a robust barrier comprising layers of closely packed keratinized cells. This dense arrangement prevents microbes from penetrating the body. The periodic shedding of epidermal cells...
Waterproofing and Anti-Bacterial Admixtures in Concrete
Concrete's susceptibility to water absorption is due to the capillary action within the pores of its hydrated cement paste. This action draws water in, creating the need for waterproofing admixtures to prevent such penetration. The efficacy of these admixtures is contingent upon the water pressure, with variations arising from different conditions such as rain, capillary rise, or hydrostatic pressure in structures intended to hold water.
Waterproofing admixtures render concrete hydrophobic,...
Waterproofing admixtures render concrete hydrophobic,...
Air-entraining Agents
Air-entraining agents improve the durability and workability of concrete in climates with frequent freezing and thawing. These agents prevent cracks by introducing small air bubbles into the mix, creating spaces accommodating water expansion when temperatures drop. The air-entraining agents lower the surface tension of water, forming stable, small air bubbles. This method is more effective than having accidental large voids, as the intentional, smaller, and evenly distributed air voids improve...


