Computational analysis of protein-protein interactions in metabolic networks of Escherichia coli and yeast.
Protein-protein interactions are operative at almost every level of cell function. In the recent years high-throughput methods have been increasingly used to uncover protein-protein interactions at genome scale resulting in interaction maps for entire organisms. However, biochemical implications of high-throughput interactions are not always obvious. The question arises whether all interactions detected by in vitro experiments also play a functional role in the living cell. In this work we systematically analyze high-throughput protein-protein interactions stored in public databases in the context of metabolic networks. Classifying reaction pairs according to their topological distance revealed a significantly higher frequency of enzyme-enzyme interactions for directly neighbored reactions (distance = 1). To determine possible functional implications for these interactions we examined randomized networks using original enzyme interactions as well as randomly generated interaction data. A functional relevance of enzyme-enzyme interactions could be demonstrated for those reactions that exhibit low connectivity. As this is a characteristic of enzyme pairs in metabolic channeling we systematically searched the literature and indeed recovered a certain fraction of enzyme pairs that has already been implicated in metabolic channeling. However, a substantial number of enzyme pairs uncovered by our large-scale analysis remains that up to now has neither been functionally nor structurally classified and therefore present novel candidates of the metabolic channeling concept.
Medical Faculty of the Humboldt University, Charite, Institute of Biochemistry, Monbijoustr. 2, 10117 Berlin, Germany. carola.huthmacher@charite.de
Carola
C
Huthmacher
Christoph
C
Gille
Hermann-Georg
HG
Holzhütter
D019295:Computational Biology; D030562:Databases, Protein; D004798:Enzymes / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
D004798:Enzymes; D029968:Escherichia coli Proteins; D029701:Saccharomyces cerevisiae Proteins