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Science 18 September 2009:
Vol. 325. no. 5947, pp. 1544 - 1549
DOI: 10.1126/science.1174671
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Reports
Three-Dimensional Structural View of the Central Metabolic Network of Thermotoga maritima
Ying Zhang,1,*
Ines Thiele,2,*,
Dana Weekes,3
Zhanwen Li,1
Lukasz Jaroszewski,3
Krzysztof Ginalski,4
Ashley M. Deacon,5
John Wooley,6
Scott A. Lesley,7
Ian A. Wilson,8
Bernhard Palsson,2
Andrei Osterman,9
Adam Godzik1,3,6,
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.
2 Department of Bioengineering, University of California at San Diego, La Jolla, CA 92093–0412, USA.
3 Joint Center for Structural Genomics (JCSG), Bioinformatics Core, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
4 Interdisciplinary Centre for Mathematical and Computational Modelling, Warsaw University, Warsaw, Poland.
5 JCSG, Structure Determination Core, Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, CA 94025, USA.
6 JCSG, Bioinformatics Core, University of California at San Diego, La Jolla, CA 92093, USA.
7 JCSG, Crystallomics Core, Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.
8 JCSG, The Scripps Research Institute, La Jolla, CA 92037, USA.
9 Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
* These authors contributed equally to this work.
 Present address: Center of Systems Biology, University of Iceland, IS-101 Reykjavik, Iceland.
| To whom correspondence should be addressed. E-mail: adam{at}burnham.org
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