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Research Themes Drug discovery

Bacterial Phosphotransferase System

SBKB [doi:10.3942/psi_sgkb/fm_2012_10]
Featured System - October 2012
Short description: Bacteria are thrifty cells.

Bacteria are thrifty cells. They often live in inhospitable environments, and many live in places with no oxygen, so their options for generating energy are limited. So, bacteria have developed many clever ways of living off of whatever is available, and exploiting these resources to their best advantage. The bacterial phosphotransferase system, often abbreviated as "PTS", is a perfect example of both the opportunistic nature of bacterial life, and their thrifty use of resources.

Harvesting Resources

The phosphotransferase system is built around a collection of specific transporters that import resources into the cell. PSI researchers at NYCOMPS have recently revealed the structure of one of these transporters, shown here from PDB entry 3qnq, which imports a disaccharide. Typical bacterial cells make many similar transporters (E. coli has at least 15) that all stand ready to import whatever sugars are available. A complex regulatory network decides which transporters are expressed and used at any given time.

Self-priming Pump

The phosphotransferase system is also particularly energy-efficient when compared to many of the other transport systems in the cell. Many transporters use ATP to power the import of nutrients, but PTS transporters also add a phosphate group to them at the same time. Instead of ATP, a molecule of phosphoenolpyruvate (one of the intermediates in glycolysis) is used to power the PTS reaction and provide the phosphate. This pre-phosphorylation of sugars primes them for entry into the energy production pathways.

Shuttling Phosphate

The phosphate group that is added to the sugar gets to the transporter in several steps. First, a dedicated central enzyme, termed EI, extracts the phosphate from phosphoenolpyruvate and adds it to a carrier protein, called HPr or "histidine protein" (shown here in a complex from PDB entry 2xdf). Then, this carrier delivers the phosphate to the whole range of different transporters. The phosphate is shuttled between several proteins, moving from HPr to EIIA to EIIB (shown here in complex from PDB entry 1vsq) and finally to the sugar in the transporter, which is known as EIIC (and sometimes with an additional chain, EIID). Each transporter is built of its own collection of EII proteins, sometimes as separate proteins and sometimes as a bunch of domains all strung together in one long protein chain.

Modular Reaction

The modular nature of the EI and EII proteins allows the same energy production machinery to power many different sugar transporters. PSI researchers have determined the structures of several different forms of the EIIB protein, from different organisms and from different sugar transport complexes. To compare some of these structures (from PDB entries 3eye, 2kyr, 2r48, 3nbm and 3p3v), the JSmol tab below displays an interactive JSmol.

EIIB Structures from PSI Researchers (PDB entries 3eye, 2kyr, 2r48, 3nbm and 3p3v)

Bacteria have a collection of different EII enzymes to import different sugars. PSI researchers have determined the structures of several EIIB proteins or domains, which provide the phosphate group that is added to the sugar during the transport. These five structures were overlapped using the Compare Structures tool at the RCSB PDB--use the buttons to compare their structures.

References

  1. Deutscher, J., Francke, C. & Postma, P. W. How phosphotransferase system-related protein phosphorylation regulates carbohydrate metabolism in bacteria. Microbiol. Mol. Biol. Rev. 70, 939-1031 (2006).

  2. Kotrba, P., Inui, M. & Yukawa, H. Bacterial phosphotransferase system (PTS) in carbohydrate uptake and control of carbon metabolism. J. Biosci. Bioengineering 92, 502-517 (2001).

References to Structures

  1. Cao, Y., et al. Crystal structure of a phosphorylation-coupled saccharide transporter. Nature 473, 50-55 (2011).

  2. Schwieters, C. D., et al. Solution structure of the 128 kDa enzyme I dimer from Escherichia coli and its 146 kDa complex with HPr using residual dipolar couplings and small- and wide-angle x-ray scattering. J. Am. Chem. Soc. 132, 13026-13045 (2010).

  3. Hu, J., et al. Solution NMR structures of productive and non-productive complexes between the A and B domains of the cytoplasmic subunit of the mannose transporter of the Escherichia coli phosphotransferase system. J. Biol. Chem. 283, 11024-11037 (2008).

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