Computational Systems Biochemistry Group

High-throughput experiments have detected a large amount of protein-protein interactions in the last years, which are catalogued in publicly accessable databases like DIP, IntAct, and MINT. In addition, different computational methods have been developed, such as the domain fusion analysis method, allowing to infer protein interactions from genome sequences. These experimentally observed and predicted interactions facilitate large scale analyses of the functional relevance of protein-protein interactions in metabolic networks.

Previous theoretical and experimental studies on multienzyme complexes have suggested that metabolic channelling may play an important role in metabolism. Direct physical interaction of enzymes catalyzing sequential reactions allows a direct transfer of a reaction intermediate to the next enzyme without releasing it into the bulk solution. This decreases the transit time of an intermediate from the active site of one enzyme to the active site of the next enzyme and, moreover, prevents the loss of intermediates which are chemically instable or possess potential toxicity. Enzyme complexes can be permanent as well as transient. A transient assembly may additionally represent a potential regulation mechanism of catalytic enzyme activity.

The objective of our study is to quantify the distance between two arbitrary metabolic enzymes based on the topology and the possible flux distributions in the metabolic network. This distance measure will then aid the process of identifying those protein associations among the large number of interactions suggested by experiments and prediction methods, which may be of functional relevance for the efficient regulation of the metabolic network.

Researchers

Carola Huthmacher
Dr. Christoph Gille
Prof. Hermann-Georg Holzhütter

Own Publications

Huthmacher C, Gille C, Holzhütter HG. (2008) A computational analysis of protein interactions in metabolic networks reveals novel enzyme pairs potentially involved in metabolic channeling. J Theor Biol., 252(3):456-64. [PubMed]

Huthmacher C, Gille C, Holzhütter HG. (2007) Computational analysis of protein-protein interactions in metabolic networks of Escherichia coli and yeast. Genome Inform., 18:162-72. [PubMed]

		Functional Relevance of Protein-Protein Interactions in Metabolic Networks
Home Research VirtualLiver People Publications Software Positions Events Contact		High-throughput experiments have detected a large amount of protein-protein interactions in the last years, which are catalogued in publicly accessable databases like DIP, IntAct, and MINT. In addition, different computational methods have been developed, such as the domain fusion analysis method, allowing to infer protein interactions from genome sequences. These experimentally observed and predicted interactions facilitate large scale analyses of the functional relevance of protein-protein interactions in metabolic networks. Previous theoretical and experimental studies on multienzyme complexes have suggested that metabolic channelling may play an important role in metabolism. Direct physical interaction of enzymes catalyzing sequential reactions allows a direct transfer of a reaction intermediate to the next enzyme without releasing it into the bulk solution. This decreases the transit time of an intermediate from the active site of one enzyme to the active site of the next enzyme and, moreover, prevents the loss of intermediates which are chemically instable or possess potential toxicity. Enzyme complexes can be permanent as well as transient. A transient assembly may additionally represent a potential regulation mechanism of catalytic enzyme activity. The objective of our study is to quantify the distance between two arbitrary metabolic enzymes based on the topology and the possible flux distributions in the metabolic network. This distance measure will then aid the process of identifying those protein associations among the large number of interactions suggested by experiments and prediction methods, which may be of functional relevance for the efficient regulation of the metabolic network. Researchers Carola Huthmacher Dr. Christoph Gille Prof. Hermann-Georg Holzhütter Own Publications Huthmacher C, Gille C, Holzhütter HG. (2008) A computational analysis of protein interactions in metabolic networks reveals novel enzyme pairs potentially involved in metabolic channeling. J Theor Biol., 252(3):456-64. [PubMed] Huthmacher C, Gille C, Holzhütter HG. (2007) Computational analysis of protein-protein interactions in metabolic networks of Escherichia coli and yeast. Genome Inform., 18:162-72. [PubMed]