リドックス・パートナー・バインディングがシトクロームP450の構成動態に与える影響

Dipanwita Batabyal¹, Logan S Richards¹, Thomas L Poulos¹

¹Departments of Molecular Biology and Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California , Irvine, California 92697-3900, United States.

Journal of the American Chemical Society

|August 22, 2017

まとめ

サイトクロームP450カムには,プチダレドキシン (Pdx) が必要である. Pdx結合は活性部位を安定させ,酸素活性化に必要な陽子リレーを可能にします.

科学分野:

生物化学
酵素学
構造生物学

背景:

プチダレドキシン (Pdx) を含むサイトクロームP450カム (P450cam) の結晶構造は,開いた形状を示している.
Pdx結合は,陽子リレーネットワーク経由でO2活性化のためにAsp251を解放すると仮定されている.
オープン状態の緩やかな基板の相互作用は,観察された水酸化選択性と矛盾しています.

研究の目的:

P450camのPdx結合によって誘発される形状の変化を調査する.
オープンコンフォームと基板結合と触媒活性を調和させる.
Pdx依存の触媒におけるAsp251の役割を明らかにする.

主な方法:

P450cam-Pdx相互作用の分子ダイナミクスシミュレーション
ワイルドタイプとR186A変異体P450camの酵素活性測定
結合したP450カムのX線結晶図

主要な成果:

Pdx結合は,活性部位を安定させ,カンファーの移動性を減少させる形状を好みます.
陽子リレーネットワークと互換性のある部分的にオープンな形状が維持されます.
R186A変異体は Pdxなしの活性を示しており,Asp251の放出が重要なことを示しています.
X線構造はR186A変異体との結合を確認した.

結論:

Pdx結合はP450カムの活性部位を安定させ,同時にO2活性化のための陽子リレーを容易にする.
塩橋からのAsp251の放出はP450カムの機能に不可欠です.
これらの発見は,P450カム触媒における陽子結合電子移転を可能にするPdxの役割を支持する.

さらに関連する動画

10:24

Defining Hsp33's Redox-regulated Chaperone Activity and Mapping Conformational Changes on Hsp33 Using Hydrogen-deuterium Exchange Mass Spectrometry

Published on: June 7, 2018

9.3K

10:01

Protein Film Infrared Electrochemistry Demonstrated for Study of H2 Oxidation by a [NiFe] Hydrogenase

Published on: December 4, 2017

12.8K

関連する概念動画

01:24

Redox Reactions

59.0K

Oxidation-reduction or redox reactions involve the transfer of electrons from one molecule or atom to another. When an atom gains an electron, another atom must lose an electron, meaning oxidation and reduction must occur together. Since the redox occurs in pairs, the atom that gets oxidized is also called the reducing agent or reductant, and the atom that is reduced is also called the oxidizing agent or oxidant. A straightforward way to remember the definitions of oxidation and reduction is...

59.0K

01:27

Redox Reactions

1.2K

Redox reactions are vital biochemical processes that underpin energy metabolism in cells. These reactions involve the transfer of electrons between molecules, occurring in tandem as oxidation and reduction. Oxidation refers to the loss of electrons, while reduction denotes their gain. This coupling ensures the seamless flow of electrons through metabolic pathways. For example, in bacterial metabolism, glucose undergoes oxidation to carbon dioxide, while oxygen is simultaneously reduced to...

1.2K

01:23

Redox Equilibria: Overview

1.6K

A reduction-oxidation reaction is commonly called a redox reaction. In a redox reaction, electrons are transferred from one species to another rather than being shared between or among atoms. The reducing agent or reductant is the species that loses electrons and gets oxidized in the process. The species that gains electrons and gets reduced in the process is the oxidizing agent or oxidant. Redox reactions are represented as two separate equations called half-reactions, where one equation...

1.6K

01:17

Oxidation of Phenols to Quinones

4.9K

In the presence of oxidizing agents, phenols are oxidized to quinones. Quinones can be easily reduced back to phenols using mild reducing agents. The electron-donating hydroxyl group enhances the reactivity of the aromatic ring, enabling oxidation of the ring even in the absence of an α hydrogen.
o-hydroxy phenols are oxidized to o-quinones and p-hydroxy phenols to p-quinones. Such redox reactions involve the transfer of two electrons and two protons. The reversible redox...

4.9K

01:58

Cooperative Allosteric Transitions

9.1K

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...