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Gewählte Publikation:

Müllebner, A; Patel, A; Stamberg, W; Staniek, K; Rosenau, T; Netscher, T; Gille, L.
(2010): Modulation of the mitochondrial cytochrome bc1 complex activity by chromanols and related compounds.
Chem Res Toxicol. 2010; 23(1):193-202 FullText FullText_BOKU

Abstract:
Tocopherols (alpha-, beta-, gamma- and delta-Toc) and tocopheryl quinones (alpha-, beta-, gamma-, and delta-TQ) were recently suggested to modulate mitochondrial electron transfer in mammals. Intriguingly, Tocs and stigmatellin, it potent inhibitor of the mitochondrial cytochrome (cyt) bc(1) complex, possess it common structural feature: the chroman core. Therefore, We studied the interference of Tocs as well as synthetic model compounds (low molecular weight TQ analogues and tetramethyl chromanones) at the mitochondrial cyt be, complex. Enzymatic experiments revealed that besides the inhibitor stigmatellin, among natural vitamin E-related derivatives, gamma-TQ/delta-TQ and, among synthetic compounds, TMC2O (6-hydroxy-4,4,7,8-tetramethylchroman-2-one) were most effective in decreasing the cyt be, activities. Stopped-flow photometric and low-temperature electron paramagnetic resonance spectroscopic experiments showed for TMC2O an inhibition of electron transfer to cyt cl and a modulation of the environment of the Rieske iron-sulfur protein (ISP). Docking experiments suggest a binding interaction of the 6-OH group and 1-O atom/2-C(=O) group of TMC2O with Glu-271 (cyt b) and His-161 (ISP) in the cyt bc(1) complex, respectively. This binding pose is similar but not identical to the potent inhibitor stgmatellin. The data Suggest that chroman-2-ones are possible templates for modulatory molecules for the cyt bc(1) target.
Autor*innen der BOKU Wien:
Rosenau Thomas
BOKU Gendermonitor:

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Electron Spin Resonance Spectroscopy -
Electron Transport - drug effects
Electron Transport Complex III - antagonists & inhibitors
Tocopherols - chemistry
Vitamin E - analogs & derivatives



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