[Research Interests] [Representative Publications] [Lab Members] RESEARCH INTERESTSFunction of Cell Membranes in Cell Recognition and Sugar TransportWe are working on three overlapping projects, all of which deal with cell surfaces and the mechanisms by which signals are transmitted from the environment to the intracellular metabolic machinery and to the genome. A bacterial phosphotransferase system (PTS) discovered in this laboratory simultaneously phosphorylates and translocates its sugar substrates across the membrane. The ultimate phosphoryl donor is phosphoenolpyruvate, and the phosphoryl group is transferred from one protein of the PTS to another until it is finally transferred to a sugar substrate, such as glucose. The phosphoryl group is linked to His residues in the proteins, and the bonds are “high energy”, about twice that of ATP. The PTS has many functions in addition to sugar transport; it regulates chemotaxis toward its substrates, the transport of other solutes, adenylate cyclase, and the transcription of certain operons. The PTS itself is stringently regulated; the thermodynamic driving force for sugar uptake is so great that the cell would burst with accumulated sugar-P if the PTS were not controlled. Our current studies are concerned with genetic and metabolic regulation of the PTS, and how it regulates other systems. Chitin, a polymer of N-acetylglucosamine (GlcNAc), is one of the most abundant organic substances in nature, and a constant rain of this highly insoluble polysaccharide falls to the ocean bottoms (in the exoskeletons of zooplankton, etc.). However, marine sediments contain little chitin, primarily because of the action of marine chitinolytic bacteria. Despite five decades of study, the mechanisms by which the insoluble polymer is converted to internal glycolytic intermediates are unknown, and are under study here, using a marine Vibrio. Each step in the process is remarkably complex, indicating how sophisticated these organisms are in their constant search for nutrients. The adhesion/deadhesion apparatus permits the organism to bind to chitin analogues, but only as long as continuous protein synthesis can be maintained (providing, in fact, a nutrient sensorium). The cells are chemotactic to chitin oligosaccharides, and degrade these oligomers to GlcNAc within the periplasmic space, thereby conserving all of the nutrient carbon. They transport GlcNAc via the PTS. These studies have broad implications for at least the marine ecosystems. Cell-cell recognition and specific intercellular adhesion are essential to normal embryonic development and morphogenesis, for example in the brain. We are attempting to define the molecular events underlying these complex phenomena using hepatocytes isolated from young rats and chicken.
REPRESENTATIVE PUBLICATIONSLi, X., Comb, D., and Roseman, S. 2009. Vibrio mutants that convert chitin containing waste products to N-acetylglucosamine and glucosamine. (A Provisional Patent Application has been filed). Jung, B-O., Roseman, S., and Park, J.K. 2008. The central concept for chitin catabolic cascade in marine bacterium, Vibrios. Macromolecular Research. 16:1-5. Li, X., Wang, L-X., Wang, X., Roseman, S. 2007. The Chitin Catabolic Cascade in the Marine Bacterium Vibrio Cholerae: Characterization of a Unique Chitin Oligosaccharide Deacetylase. Glycobiology. 17:1377-1387. Patel, H.V., Vyas, K.A., Savtchenko, R., and Roseman, S. 2006. The monomer/dimer transition of enzyme I of the Escherichia coli phosphotransferase system. J Biol Chem. 281(26):17570-8. Epub 2006 Mar 19. Meibom, K.L., Li, X.B., Nielsen, A.T., Wu, C.Y., Roseman, S., and Schoolnik, G.K. 2004. The Vibrio cholerae chitin utilization program. Proc Natl Acad Sci U S A. 101(8):2524-9. Park, J.K. and Roseman, S. 2001. Molecular Cloning and Characterization of a Unique b-Glucosidase from Vibrio cholerae. J.Biol.Chem., to be submitted. Roseman, S. 2001. Reflections on glycobiology. J.Biol.Chem., 276, 41527-41542. Park, J. K., Wang, L.-X. & Roseman, S. (2002) Isolation of a Glucosamine-Specific Kinase, a Unique Enzyme of Vibrio cholerae. J.Biol.Chem., 277, 15573-15578 Holtman, C.K., Pawlyk, A.C., Meadow, N.D., Roseman, S., and Pettigrew, D.W. 2001. IIAGlc allosteric control of Escherichia coli glycerol kinase: binding site cooperative transitions and cation-promoted association by Zinc(II). Biochemistry, 40, 14302-14308. Rohwer, J.M., Meadow, N.D., Roseman, S., Westerhoff, H. V., and Postma, P. W. 2000. Understanding glucose transport by the bacterial phosphoenolpyruvate:glycose phosphotransferase system on the basis of kinetic measurements in vitro. J. Biol. Chem., 275, 34909-34921 Keyhani, N.O., Rodgers, M.E., Demeler, B., Hansen, J.C., and Roseman, S. 2000. Analytical sedimentation of the IIAChb and IIBChb Proteins of the Escherichia coli N,N'-Diacetylchitobiose Phosphotransferase System: Demonstration of a Model Phosphotransfer Transition State Complex. J. Biol. Chem., 275, 33110-33115 Keyhani, N.O., Bacia, K., and Roseman, S. 2000. The Transport/Phosphorylation of N,N'-diacetylchitobiose in Escherichia coli: Characterization of Phospho-IIBChb and of a Potential Transition State Analogue in the Phosphotransfer Reactions Between the Proteins IIAChb and IIBChb. J. Biol. Chem., 275, 33102-33109. Keyhani, N.O., Boudker, O., and Roseman, S. 2000. Isolation and Characterization of IIAChb, A Soluble Protein of the Enzyme II Complex Required for the Transport/Phosphorylation of N,N'-Diacetylchitobiose in Escherichia coli. J. Biol. Chem., 27533091-33101.Keyhani, N.O., Wang, L-X., Lee, Y.C., and Roseman, S. 2000. The Chitin Disaccharide, N,N'-Diacetylchitobiose, is Catabolized by Escherichia coli, and is Transported/Phosphorylated by the Phosphoenolpyruvate:glycose Phosphotransferase System. J. Biol. Chem., 275, 33084-33090. Park, J. K., Keyhani, N. O., and Roseman, S. 2000. Chitin Catabolic Cascade in the Marine Bacterium Vibrio furnissii: Identification, Molecular Cloning, and Characterization of a N,N'-Diacetylchitobiose Phosphorylase. J. Biol. Chem., 275, 33077-33083. Keyhani, N.O., Li, X., and Roseman, S. 2000. Chitin Catabolism in the Marine Bacterium Vibrio furnissii: Identification and Molecular Cloning of a Chitoporin. J. Biol. Chem., 275, 33068-33076. Lab Members
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