Three-Dimensional Structural View of the Central Metabolic Network of Thermotoga maritima

Now Shown in 3D With the advent of systems-wide technologies and the development of analytical methods, data produced by analyzing individual or small groups of molecular components can be integrated to reassemble whole biological systems. Zhang et al. (p. 1544) have undertaken a major technological challenge: to integrate biochemical data with experimentally determined or predicted three-dimensional structures of all proteins involved in the central metabolism of a bacterial cell. This integration of large-scale data sets provides evolutionary and functional insights and furthers our understanding of the molecular assembly of complex biological networks. Protein structure and biochemical data generate a three-dimensional view of the metabolic network of a bacterial cell. Metabolic pathways have traditionally been described in terms of biochemical reactions and metabolites. With the use of structural genomics and systems biology, we generated a three-dimensional reconstruction of the central metabolic network of the bacterium Thermotoga maritima. The network encompassed 478 proteins, of which 120 were determined by experiment and 358 were modeled. Structural analysis revealed that proteins forming the network are dominated by a small number (only 182) of basic shapes (folds) performing diverse but mostly related functions. Most of these folds are already present in the essential core (~30%) of the network, and its expansion by nonessential proteins is achieved with relatively few additional folds. Thus, integration of structural data with networks analysis generates insight into the function, mechanism, and evolution of biological networks.