3NA1

Crystal structure of human CYP11A1 in complex with 20-hydroxycholesterol

3NA1 の概要

• エントリーDOI: 10.2210/pdb3na1/pdb
• 関連するPDBエントリー: 3N9Y 3N9Z 3NA0
• 分子名称: Cholesterol side-chain cleavage enzyme, mitochondrial, Adrenodoxin, mitochondrial, PROTOPORPHYRIN IX CONTAINING FE, ... (6 entities in total)
• 機能のキーワード: cytochrome p450, 20-hydroxycholesterol, cholesterol side chain cleavage, structural genomics, structural genomics consortium, sgc, oxidoreductase, electron transport
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Mitochondrion membrane: P05108; Mitochondrion matrix : P10109
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 143136.12

構造登録者

Strushkevich, N.V.,MacKenzie, F.,Tempel, W.,Botchkarev, A.,Arrowsmith, C.H.,Edwards, A.M.,Bountra, C.,Weigelt, J.U.,Park, H.,Structural Genomics Consortium (SGC) (登録日: 2010-05-31, 公開日: 2011-06-08, 最終更新日: 2023-09-06)

主引用文献

Strushkevich, N.,Mackenzie, F.,Cherkesova, T.,Grabovec, I.,Usanov, S.,Park, H.W.
Structural basis for pregnenolone biosynthesis by the mitochondrial monooxygenase system.
Proc.Natl.Acad.Sci.USA, 108:10139-10143, 2011

PubMed Abstract: In humans, the precursor to all steroid hormones, pregnenolone, is synthesized from cholesterol by an enzyme complex comprising adrenodoxin reductase (AdR), adrenodoxin (Adx), and a cytochrome P450 (P450scc or CYP11A1). This complex not only plays a key role in steroidogenesis, but also has long been a model to study electron transfer, multistep catalysis, and C-C bond cleavage performed by monooxygenases. Detailed mechanistic understanding of these processes has been hindered by a lack of structural information. Here we present the crystal structure of the complex of human Adx and CYP11A1--the first of a complex between a eukaryotic CYP and its redox partner. The structures with substrate and a series of reaction intermediates allow us to define the mechanism underlying sequential hydroxylations of the cholesterol and suggest the mechanism of C-C bond cleavage. In the complex the [2Fe-2S] cluster of Adx is positioned 17.4 Å away from the heme iron of CYP11A1. This structure suggests that after an initial protein-protein association driven by electrostatic forces, the complex adopts an optimized geometry between the redox centers. Conservation of the interaction interface suggests that this mechanism is common for all mitochondrial P450s.

PubMed: 21636783
DOI: 10.1073/pnas.1019441108

実験手法

X-RAY DIFFRACTION (2.25 Å)