4WPZ

Crystal structure of cytochrome P450 CYP107W1 from Streptomyces avermitilis

4WPZ の概要

• エントリーDOI: 10.2210/pdb4wpz/pdb
• 関連するPDBエントリー: 4WQ0
• 分子名称: Cytochrome P450, POTASSIUM ION, PROTOPORPHYRIN IX CONTAINING FE, ... (4 entities in total)
• 機能のキーワード: p450, cyp, cyp107w1, streptomyces avermitilis, oligomycin, oxidoreductase
• 由来する生物種: Streptomyces avermitilis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44041.23

構造登録者

Kang, L.W.,Kim, D.H.,Pham, T.V.,Han, S.H. (登録日: 2014-10-21, 公開日: 2015-04-22, 最終更新日: 2024-11-06)

主引用文献

Han, S.,Pham, T.V.,Kim, J.H.,Lim, Y.R.,Park, H.G.,Cha, G.S.,Yun, C.H.,Chun, Y.J.,Kang, L.W.,Kim, D.
Functional characterization of CYP107W1 from Streptomyces avermitilis and biosynthesis of macrolide oligomycin A.
Arch.Biochem.Biophys., 575:1-7, 2015

PubMed Abstract: Streptomyces avermitilis contains 33 cytochrome P450 genes in its genome, many of which play important roles in the biosynthesis process of antimicrobial agents. Here, we characterized the biochemical function and structure of CYP107W1 from S. avermitilis, which is responsible for the 12-hydroxylation reaction of oligomycin C. CYP107W1 was expressed and purified from Escherichia coli. Purified proteins exhibited the typical CO-binding spectrum of P450. Interaction of oligomycin C and oligomycin A (12-hydroxylated oligomycin C) with purified CYP107W1 resulted in a type I binding with Kd values of 14.4 ± 0.7 μM and 2.0 ± 0.1 μM, respectively. LC-mass spectrometry analysis showed that CYP107W1 produced oligomycin A by regioselectively hydroxylating C12 of oligomycin C. Steady-state kinetic analysis yielded a kcat value of 0.2 min(-1) and a Km value of 18 μM. The crystal structure of CYP107W1 was determined at 2.1 Å resolution. The overall P450 folding conformations are well conserved, and the open access binding pocket for the large macrolide oligomycin C was observed above the distal side of heme. This study of CYP107W1 can help a better understanding of clinically important P450 enzymes as well as their optimization and engineering for synthesizing novel antibacterial agents and other pharmaceutically important compounds.

PubMed: 25849761
DOI: 10.1016/j.abb.2015.03.025

実験手法

X-RAY DIFFRACTION (2.1 Å)