2XN8

X-RAY STRUCTURE OF THE SUBSTRATE-FREE MYCOBACTERIUM TUBERCULOSIS CYTOCHROME P450 CYP125

2XN8 の概要

• エントリーDOI: 10.2210/pdb2xn8/pdb
• 関連するPDBエントリー: 2X5L 2X5W 2XC3
• 分子名称: PUTATIVE CYTOCHROME P450 125, SULFATE ION, PROTOPORPHYRIN IX CONTAINING FE, ... (4 entities in total)
• 機能のキーワード: cholesterol degradation, reverse type i inhibitor, monooxygenase, oxidoreductase
• 由来する生物種: MYCOBACTERIUM TUBERCULOSIS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48174.87

構造登録者

Ouellet, H.,Kells, P.M.,Ortiz de Montellano, P.R.,Podust, L.M. (登録日: 2010-07-30, 公開日: 2010-11-10, 最終更新日: 2023-12-20)

主引用文献

Ouellet, H.,Kells, P.M.,Ortiz de Montellano, P.R.,Podust, L.M.
Reverse Type I Inhibitor of Mycobacteriumtuberculosis Cyp125A1.
Bioorg.Med.Chem.Lett., 21:332-, 2011

PubMed Abstract: Cytochrome P450 CYP125A1 of Mycobacterium tuberculosis, a potential therapeutic target for tuberculosis in humans, initiates degradation of the aliphatic chain of host cholesterol and is essential for establishing M. tuberculosis infection in a mouse model of disease. We explored the interactions of CYP125A1 with a reverse type I inhibitor by X-ray structure analysis and UV-vis spectroscopy. Compound LP10 (α-[(4-methylcyclohexyl)carbonyl amino]-N-4-pyridinyl-1H-indole-3-propanamide), previously identified as a potent type II inhibitor of Trypanosomacruzi CYP51, shifts CYP125A1 to a water-coordinated low-spin state upon binding with low micromolar affinity. When LP10 is present in the active site, the crystal structure and spectral characteristics both demonstrate changes in lipophilic and electronic properties favoring coordination of the iron axial water ligand. These results provide an insight into the structural requirements for developing selective CYP125A1 inhibitors.

PubMed: 21109436
DOI: 10.1016/J.BMCL.2010.11.007

実験手法

X-RAY DIFFRACTION (1.64 Å)