What question did this study set out to answer?

Determine the molecular mechanism of atovaquone binding to the cytochrome bc1 complex and identify the structural features governing species-specific drug sensitivity.

August 1, 2003Journal of Biological ChemistryOpen Access

Molecular Basis for Atovaquone Binding to the Cytochrome bc 1 Complex

View Full Paper

Ask AI

Bookmark

Determine the molecular mechanism of atovaquone binding to the cytochrome bc1 complex and identify the structural features governing species-specific drug sensitivity.
Assayed the inhibition kinetics, midpoint redox potentials, and electron paramagnetic resonance (EPR) spectra of the bc1 complex isolated from Saccharomyces cerevisiae.
Generated energy-minimized ligand-docking models and introduced an L275F mutation into yeast cytochrome b to mimic the mammalian sequence.
Atovaquone competitively inhibited the yeast bc1 complex with an apparent Ki of 9 nM, shifted Rieske center EPR g values, and increased the Rieske iron-sulfur protein midpoint potential from 285 to 385 mV.
The bovine enzyme displayed reduced sensitivity (Ki = 80 nM), and the yeast L275F mutant mirrored this resistance phenotype with a Ki of 100 nM without altering baseline enzymatic activity.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Biochemical study reveals how atovaquone binds the fungal cytochrome bc1 complex, highlighting the molecular basis for species-selective inhibition.

Cite This Study

Kessl et al. (2003) studied this question.

synapsesocial.com/papers/6a8520cdf76e40547ac2a407 https://doi.org/10.1074/jbc.m304042200

View Full Paper

Ask AI

Bookmark

Implication

Biochemical study reveals how atovaquone binds the fungal cytochrome bc1 complex, highlighting the molecular basis for species-selective inhibition.

Molecular Basis for Atovaquone Binding to the Cytochrome bc 1 Complex

Key Points

Discussion

Implication

Cite This Study

Molecular Basis for Atovaquone Binding to the Cytochrome bc 1 Complex

Key Points

Discussion

Implication

Cite This Study

Also Consider

Also Consider