熱力学と,ナトリウム結合アスパラジンのデアミデーションのメカニズム
1Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
Journal of the American Chemical Society
|July 11, 2008
まとめ
アスパラジン (Asn) のデアミデーションは,一般的なタンパク質の改変であり,質量スペクトロメトリと量子計算を使用して分子的に記述されました. 速度を制限するステップは1.61 eVを必要とし,周期的なサクシン環を形成します.
科学分野:
- バイオケミストリー バイオケミストリー
- 化学物理 化学物理
- コンピューティング・ケミストリー
背景:
- アスパラジン (Asn) のデアミデーションは,翻訳後の頻繁に起こる変化です.
- この変異は,老化,炎症,退行性疾患に関与しています.
研究 の 目的:
- Asnデアミデーションの包括的な分子説明を提供するために.
- 反応機構を解明し,Na(+) ((Asn) 複合体の速度制限ステップを特定する.
主な方法:
- 誘導イオンビームタンデム質量スペクトロメトリ (GIBMS) は,XEとの衝突誘発解離 (CID) を研究するために使用されました.
- エネルギーに依存するCIDの横断断面の高度な分析は,競合するおよび連続したプロセスを考慮した.
- 量子化学計算 (B3LYP,MP2) を用いて,移行状態と中間物質を特定しました.
主要な成果:
- Asnのデアミデーションの0Kバリアは,様々な実験的および理論的要因を考慮して決定されました.
- 潜在エネルギー表面スキャンは,主要な反応種と移行状態を特定しました.
- 速度を制限するステップは,周期的なサクシン状のリング構造の形成であると特定されました.
結論:
- この研究は,Na (((+)) (((Asn)) のデアミド化における基本的なステップの完全な特徴づけを提供します.
- 速度制限のステップには1.61 ± 0.08 eVが必要です.
- この研究は,様々な病気に関連する重要なタンパク質の改変に関する分子洞察を提供します.
関連する概念動画
1° Amines to Diazonium or Aryldiazonium Salts: Diazotization with NaNO2 Mechanism
Nitrous acid is a relatively weak and unstable acid prepared in situ by the reaction of sodium nitrite and cold, dilute hydrochloric acid. In an acidic solution, the nitrous acid undergoes protonation when it loses water to form a nitrosonium ion—an electrophile. Nitrous acid reacts with primary amines to give diazonium salts. The reaction is called diazotization of primary amines.
Aldehydes and Ketones with Amines: Imine Formation Mechanism
Imine formation involves the addition of carbonyl compounds to a primary amine. It begins with the generation of carbinolamine through a series of steps involving an initial nucleophilic attack and then several proton transfer reactions. The second part includes the elimination of water, as a leaving group, to give the imine.
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
Imines are formed under mildly acidic conditions. A pH of 4.5 is ideal for the reaction.
If the pH is low or the solution is too acidic, the reaction slows down in the...
Aldehydes and Ketones with Amines: Enamine Formation Mechanism
Enamine formation involves the addition of carbonyl compounds to a secondary amine through a series of reactions. The mechanism begins with the generation of carbinolamine, a nucleophilic attack followed by several proton transfer reactions. The hydroxyl group of the carbinolamine is converted into water to make a better leaving group that can push the reaction forward by eliminating a water molecule. In enamine formation, the last step involves the abstraction of a proton from the α carbon to...
2° Amines to N-Nitrosamines: Reaction with NaNO2
Secondary amines react with nitrous acid to form N-nitrosamines, as depicted in Figure 1. Nitrous acid, a weak and unstable acid, is formed in situ from an aqueous solution of sodium nitrite and strong acids, such as hydrochloric acid or sulfuric acid, in cold conditions. In the presence of an acid, the nitrous acid gets protonated. The subsequent loss of water results in the formation of the electrophile known as nitrosonium ion.
Amides to Carboxylic Acids: Hydrolysis
Amides can undergo either acid-catalyzed hydrolysis or base-promoted hydrolysis through a typical nucleophilic acyl substitution. Each hydrolysis requires severe conditions.
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
Acid-catalyzed hydrolysis:
Hydrolysis of amides under acidic conditions yields carboxylic acids. Since the reaction occurs slowly, hydrolysis requires the conditions of heat.
The mechanism begins with the protonation of the carbonyl oxygen by the acid catalyst. The protonation makes the amide carbonyl carbon more...
Acid Halides to Amides: Aminolysis
Aminolysis is a nucleophilic acyl substitution reaction, where ammonia or amines act as nucleophiles to give the substitution product. Acid halides react with ammonia, primary amines, and secondary amines to yield primary, secondary, and tertiary amides, respectively.
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...
In the first step of the aminolysis mechanism, the amine attacks the carbonyl carbon of the acyl chloride to form a tetrahedral intermediate. In the second step, the carbonyl group is re-formed with the elimination of a chloride...


