Investigators at Burnham Institute for Medical Research (Burnham), University of California, San Diego (UC San Diego), The Scripps Research Institute (TSRI), Genomics Institute of the Novartis Research Foundation (GNF) and other institutions have constructed a complete model, including three dimensional protein structures, of the central metabolic network of the bacterium Thermotoga maritima (T. maritima).
This is the first time scientists have developed such a comprehensive model of a metabolic network overlaid with an atomic resolution of network proteins. The analysis of the model, among others, highlights the important role of a small number of essential protein shapes, lending new insights into the evolution of protein networks and the functions within these networks. The study was published in the journal Science on September 18.
Combining biochemical studies, structural genomics and computer modeling, the researchers deciphered the shapes, functions and interactions of 478 proteins that make up T. maritima’s central metabolism. The team also found connections between these proteins and 503 unique metabolites in 562 intracellular and 83 extracellular metabolic reactions.
“We have built an actual three dimensional model of every protein in the central metabolic system,” said Adam Godzik, Ph.D., director of Burnham’s Bioinformatics and Systems Biology program. “We got the whole thing. This is analogous to sequencing an entire genome.”
With this data, scientists can simulate metabolism simultaneously on a biochemical and molecular level. This information has the promise to expand computer modeling to allow investigators to simulate the interactions between proteins and various compounds in an entire system. Furthermore, the procedure developed in this study could be applied to study many other organisms, including humans. It could potentially help identify both positive and adverse drug reactions before pre-clinical and clinical trials. The research may also have applications in energy research, as bacteria like T. maritima can be engineered to more efficiently produce hydrogen, a key source of clean energy.
“In addition to the systematic analysis of interacting components, the next challenge is addressing the levels or scales of biological organization, ranging from molecules to an individual and even to populations,” said co-author John C. Wooley, Ph.D., of UC San Diego’s Center for Research in Biological Systems and the California Institute for Telecommunications and Information Technology. “This work, by including both functional and architectural details, takes that first step and provides a novel, enriched view of the complexity of life.”
Researchers were surprised by the degree of structural conservation within the network. Of the 478 proteins, with 714 domains, there were only 182 distinct folds. This supports the hypothesis that nature uses existing shapes, slightly modified, to perform new tasks.
The team used genomic, metabolic, and structural reconstruction to determine the network down to the atomic level. They then classified metabolic reactions based on whether they were similar, connected or unrelated and found that enzymes that catalyze similar reactions have a higher probability of having similar folds. In addition, using a reductive evolution simulation approach, they uncovered the absolutely essential proteins to support a minimal viable network.
“We were able to put together the information from the network biology as well as the protein structural biology,” said co-author Bernhard Palsson, Ph.D., a UC San Diego bioengineering professor who leads the Systems Biology Research Group. “This is the first time this has been accomplished. We are in a position to study microorganisms in much greater detail, including those that are important in health care and those that are of environmental concern.”
This work was funded by grants from the National Institute of General Medical Sciences and the Office of Biological and Environmental Research within the U.S. Department of Energy's Office of Science.About Burnham Institute for Medical Research
Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Burnham is a nonprofit public benefit corporation.About the University of California, San Diego
Josh Baxt | Newswise Science News
Further reports about: > Medical Wellness > Science TV > Scripps > Telecommunication > computer model > computer modeling > drug discovery > essential protein shapes > extracellular metabolic reactions > information technology > medical research > metabolic disorders > metabolic network > molecular level > protein structure > structural reconstruction > synthetic biology
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy