title: Reactive oxygen species target specific tryptophan site in the mitochondrial ATP synthase.
abstract: The release of reactive oxygen species (ROS) as side products of aerobic metabolism in the mitochondria is an unavoidable consequence. As the capacity of organisms to deal with this exposure declines with age, accumulation of molecular damage caused by ROS has been defined as one of the central events during the ageing process in biological systems as well as in numerous diseases such as Alzheimer's and Parkinson's Dementia. In the filamentous fungus Podospora anserina, an ageing model with a clear defined mitochondrial etiology of ageing, in addition to the mitochondrial aconitase the ATP synthase alpha subunit was defined recently as a hot spot for oxidative modifications induced by ROS. In this report we show, that this reactivity is not randomly distributed over the ATP Synthase, but is channeled to a single tryptophan residue 503. This residue serves as an intra-molecular quencher for oxidative species and might also be involved in the metabolic perception of oxidative stress or regulation of enzyme activity. A putative metal binding site in the proximity of this tryptophan residue appears to be crucial for the molecular mechanism for the selective targeting of oxidative damage.
authors: Ruhr University Bochum, Bochum, Germany. sascha.rexroth@rub.de
authors: Sascha
authors: S
authors: Rexroth
authors: Ansgar
authors: A
authors: Poetsch
authors: Matthias
authors: M
authors: Rögner
authors: Andrea
authors: A
authors: Hamann
authors: Alexandra
authors: A
authors: Werner
authors: Heinz D
authors: HD
authors: Osiewacz
authors: Eva R
authors: ER
authors: Schäfer
authors: Holger
authors: H
authors: Seelert
authors: Norbert A
authors: NA
authors: Dencher
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D016503:Drug Delivery Systems; D025261:Mitochondrial Proton-Translocating ATPases / Q000737:chemistry* / Q000378:metabolism*; D008954:Models, Biological; D008958:Models, Molecular; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology; D048468:Podospora / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects / Q000502:physiology; D020836:Protein Structure, Quaternary; D017433:Protein Structure, Secondary; D017382:Reactive Oxygen Species / Q000378:metabolism / Q000494:pharmacology*; D013379:Substrate Specificity; D014364:Tryptophan / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D014364:Tryptophan; D025261:Mitochondrial Proton-Translocating ATPases