5DQN

Polyethylene 600-bound form of P450 CYP125A3 mutant from Myobacterium Smegmatis - W83Y

5DQN の概要

• エントリーDOI: 10.2210/pdb5dqn/pdb
• 関連するPDBエントリー: 4APY
• 分子名称: Cytochrome P450 CYP125, PROTOPORPHYRIN IX CONTAINING FE, PHOSPHATE ION, ... (6 entities in total)
• 機能のキーワード: oxidoreductase, cholesterol metabolism
• 由来する生物種: Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48233.57

構造登録者

Ortiz de Montellano, P.J.,Frank, D.J.,Waddling, C.A. (登録日: 2015-09-15, 公開日: 2015-11-18, 最終更新日: 2023-09-27)

主引用文献

Frank, D.J.,Waddling, C.A.,La, M.,Ortiz de Montellano, P.R.
Cytochrome P450 125A4, the Third Cholesterol C-26 Hydroxylase from Mycobacterium smegmatis.
Biochemistry, 54:6909-6916, 2015

PubMed Abstract: Mycobacterium tuberculosis (Mtb) and Mycobacterium smegmatis (Msmeg) can grow on cholesterol as the sole carbon source. In Mtb the utilization of cholesterol can be initiated by CYP125A1 or CYP142A1 and in Msmeg by the orthologous CYP125A3 and CYP142A2. Double knockout of the two enzymes in Mtb prevents its growth on cholesterol, but the double knockout of Msmeg is still able to grow, albeit at a slower rate. We report here that Msmeg has a third enzyme, CYP125A4, that also oxidizes cholesterol, although it has a much higher activity for the oxidation of 7α-hydroxycholesterol. The ability of Msmeg CYP125A4 (and Mtb CYP125A1) to oxidize 7α-hydroxycholesterol is due, at least in part, to the presence of a smaller amino acid side chain facing C-7 of the sterol substrate than in CYP125A3. The ability to oxidize 7-substituted steroids broadens the range of sterol carbon sources for growth, but even more importantly in Mtb, additional biological effects are possible due to the potent immunomodulatory activity of 7α,26-dihydroxycholesterol.

PubMed: 26522442
DOI: 10.1021/acs.biochem.5b01029

実験手法

X-RAY DIFFRACTION (2.262 Å)