The organization of metabolic reaction networks. II. Signal processing in hierarchical structured functional units.
Based on the analysis of molecular interactions of proteins with DNA binding sites, a new approach to developing mathematical models describing gene expression is introduced. Detection of hierarchical structures in metabolic networks can be used to decompose complex reaction schemes. This will be achieved by assigning each regulator protein to one level in the hierarchy. Signals are then transduced from the top level to the lower level, but not vice versa. The method is shown by a simple example with two interacting proteins. A comparison of simulation results shows good agreement between a model taking all interactions into account and a model developed with the new approach. Finally, the method is applied to the crpA modulon in Escherichia coli, which controls uptake and metabolism for a number of carbohydrates. Here, RNA polymerase represents the top level, CrpA the second level, and the lactose-specific repressor LacI the lowest level, respectively. Besides the lactose operon, the method is applied to the adenylate cyclase gene and the gene for the regulator CrpA.
Kremling
A
A
Max-Planck-Institut für Dynamik Komplexer Technischer Systeme, Magdeburg, Germany.
Gilles
E D
ED
D000249:Adenosine Monophosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D001665:Binding Sites; D002352:Carrier Proteins; D000242:Cyclic AMP / Q000494:pharmacology; D002373:Cyclic AMP Receptor Protein / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins; D007700:Kinetics; D056968:Lac Repressors; D008660:Metabolism; D008954:Models, Biological; D008956:Models, Chemical; D008962:Models, Theoretical; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction
D001426:Bacterial Proteins; D002352:Carrier Proteins; D002373:Cyclic AMP Receptor Protein; D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; D012097:Repressor Proteins; D000249:Adenosine Monophosphate; D004247:DNA; D000242:Cyclic AMP; D012321:DNA-Directed RNA Polymerases; D000262:Adenylyl Cyclases