ヘム依存型チロシンヒドロキシラーゼにおけるC-HとC-F結合活性化の分断の分子的根拠
Yifan Wang1, Ian Davis1, Inchul Shin1
1Department of Chemistry, The University of Texas at San Antonio, One UTSA Circle, Texas 78249, United States.
Journal of the American Chemical Society
|March 18, 2021
まとめ
ヘム依存のl-チロシンヒドロキシラーゼ (TyrHs) は二重C-HとC-F結合の活性化を示している. この新しい酵素ファミリーでは,基板の方向性が製品分布を決定する.
科学分野:
- 生物化学
- 酵素学
- 構造生物学
背景:
- ヘム依存型l-チロシン水酸化酵素 (TyrHs) は,非ヘム鉄酵素とは異なる新しい酵素ファミリーを表しています.
- TyrHはC-HとC-F結合の両方,特に3-フッ素-l-チロシン (3-F-Tyr) と分裂する二重反応性を示す.
- この二重反応性の根底にあるメカニズムは,ほとんど未知のままです.
研究 の 目的:
- *Streptomyces sclerotialus* (SsTyrH) の新しいTyrHを機能的かつ構造的に特徴づけること.
- ヘム依存性TyrHによる二重C-HとC-F結合活性化の分子基礎を解明する.
- TyrH触媒反応における産物分布に影響を与える要因を決定する.
主な方法:
- 高解像度 (1.89 Å,1.68 Å,1.58 Å) で酵素基板と中間構造を決定するX線結晶学.
- His88のような活性サイト残留物の役割を調査するサイト指向型変異.
- フェリック・ヒドロペロキソ介質 (化合物0) を含む反応介質の特徴を示すために,光譜分析を行う.
主要な成果:
- SsTyrHの結晶構造がl-チロシンと複合すると,電子の移転がC-H結合の水酸化を開始する.
- ミュタゲネーシスは活性部位ヒスティジン (His88) の触媒的役割を確認した.
- 3Fタイヤの構造は,基板の方向性が製品分布の主要な決定因子であることを示しました (7: 3比).
- 3F-タイヤの触媒化において,フェリック・ヒドロペロキソ中間体 (化合物0) が観察され,構造的に特徴づけられた.
結論:
- この研究は,ヘム依存のTyrH機能に関する最初の分子洞察を提供します.
- 基板結合の方向性は,C-HとC-F結合の活性化を制御する重要な要因である.
- この新しい酵素ファミリーの構造とメカニズムの理解は著しく進んでいる.
関連する概念動画
Photochemical Electrocyclic Reactions: Stereochemistry
2.0K
The absorption of UV–visible light by conjugated systems causes the promotion of an electron from the ground state to the excited state. Consequently, photochemical electrocyclic reactions proceed via the excited-state HOMO rather than the ground-state HOMO. Since the ground- and excited-state HOMOs have different symmetries, the stereochemical outcome of electrocyclic reactions depends on the mode of activation; i.e., thermal or photochemical.
Selection Rules: Photochemical Activation
Selection Rules: Photochemical Activation
2.0K
Aromatic Hydrocarbon Cations: Structural Overview
3.4K
Cycloheptatriene is a neutral monocyclic unsaturated hydrocarbon that consists of an odd number of carbon atoms and an intervening sp3 carbon in the ring. The three double bonds in the ring correspond to 6 π electrons, which is a Huckel number, and therefore satisfies the criteria of 4n + 2 π electrons. However, the intervening sp3 carbon disrupts the continuous overlap of p orbitals. As a result, cycloheptatriene is not aromatic.
Removing one hydrogen from the intervening CH2 group...
Removing one hydrogen from the intervening CH2 group...
3.4K
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
6.9K
All ortho–para directors, excluding halogens, are activating groups. These groups donate electrons to the ring, making the ring carbons electron-rich. Consequently, the reactivity of the aromatic ring towards electrophilic substitution increases. For instance, the nitration of anisole is about 10,000 times faster than the nitration of benzene. The electron-donating effect of the methoxy group in anisole activates the ortho and para positions on the ring and stabilizes the corresponding...
6.9K
Cycloaddition Reactions: MO Requirements for Photochemical Activation
2.3K
Some cycloaddition reactions are activated by heat, while others are initiated by light. For example, a [2 + 2] cycloaddition between two ethylene molecules occurs only in the presence of light. It is photochemically allowed but thermally forbidden.
2.3K
Thermal Electrocyclic Reactions: Stereochemistry
2.2K
The stereochemistry of electrocyclic reactions is strongly influenced by the orbital symmetry of the polyene HOMO. Under thermal conditions, the reaction proceeds via the ground-state HOMO.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
Selection Rules: Thermal Activation
Conjugated systems containing an even number of π-electron pairs undergo a conrotatory ring closure. For example, thermal electrocyclization of (2E,4E)-2,4-hexadiene, a conjugated diene containing two π-electron pairs, gives trans-3,4-dimethylcyclobutene.
2.2K
Woodward–Hoffmann Selection Rules and Microscopic Reversibility
3.5K
Electrocyclic reactions, cycloadditions, and sigmatropic rearrangements are concerted pericyclic reactions that proceed via a cyclic transition state. These reactions are stereospecific and regioselective. The stereochemistry of the products depends on the symmetry characteristics of the interacting orbitals and the reaction conditions. Accordingly, pericyclic reactions are classified as either symmetry-allowed or symmetry-forbidden. Woodward and Hoffmann presented the selection criteria for...
3.5K


