jacobson@bu.edu

Cell Signaling and Gene Regulation Microbial Physiology and Genetics Biochemistry

Professor of Biology
Ph.D., Stanford University, 1974

Currently my laboratory is interested in the mechanism and regulation of transmembrane sugar transport in bacteria. In our major project, we are studying the structure and mechanism of the protein responsible for the concomitant transport and phosphorylation of D-mannitol in E. coli. This protein is the mannitol-specific Enzyme II (mannitol permease) of the phosphoenolpyruvate-dependent phosphotransferase system (PTS). It has been purified and characterized, its gene (mtlA) has been cloned and sequenced, and its mechanism and topography in the membrane have been investigated. Using biochemical, biophysical and recombinant DNA techniques, we are determining both the intramembrane structure of this protein and elucidating structure-function relationships in the mannitol permease. Since this protein is multifunctional (in addition to its transport and phosphorylation functions, it also acts as the primary chemotactic receptor for mannitol), we are identifying specific parts of the molecule that are responsible for specific functions. Recently, we have constructed a large number of deletion and site-specific mutations in mtlA, as well as a number of vectors expressing several of the structural and functional domains of the permease, that have been extremely useful for this purpose. Our overall goal is to learn in as much molecular detail as possible the mechanisms of the various functions of the mannitol permease as well as the ways by which its synthesis and activities are regulated in E. coli. In the future, these studies will rely on the continued use of biochemical, biophysical (e.g. X-ray crystallography), and molecular biological techniques.

Very recently, we have discovered that the activity of a class of proteins that is involved in the regulation of nitrogen assimilation in a variety of eubacterial species may be modulated by the PTS through phosphorylation-dephosphorylation reactions. To date our evidence strongly suggests that this PTS-mediated modulation is a means by which the availability of carbon to the cell (in the form of PTS substrates) is sensed by the machinery which regulates the transcription of genes involved in nitrogen assimilation and other processes. More over, we have found that at least one protein involved in the regulation of transcription of nitrogen assimilatory genes also affects transcription of PTS genes. This would therefore provide a means by which both C and N assimilation could be coordinately controlled, especially under conditions of limiting carbon or nitrogen. This problem has broad implications in bacterial growth regulation, as well as the control of such economically important processes as bioremediaon and biological nitrogen fixation.

Jacobson GR. 2003. Review of Microbial Physiology. Moat, Foster, Spector, 4th edition. Biomol Eng. Mar;20(3):113.

Jacobson GR, Lengeler JW. 2002. Pieter W. Postma 1942-2002. Mol Microbiol. Sep;45(6):1461-2.

Cynthia A. Saraceni-Richards and Gary R. Jacobson. 1997. "Subunit and Amino Acid Interactions in the Escherichia coli Mannitol Permease: a Functional Complementation Study of Coexpressed Mutant Permease Proteins", Journal of Bacteriology 179: 5171-5177.

Cynthia A. Saraceni-Richards and Gary R. Jacobson. 1997. "A Conserved Glutamate Residue, Glu-257, Is Important for Substrate Binding and Transport by the Escherichia coli Mannitol Permease", Journal of Bacteriology 179: 1135-1142.

Pieter W. Postma, Joseph W. Lengeler and Gary R. Jacobson, "Phosphoenolpyruvate:carbohydrate phosphotransferase systems", in Escherichia coli and Salmonella typhimurium, 2nd edn., ASM Press, Waashington, D.C., pp. 1149-1174, 1996.

Gail S. Begley, Kimberly A. Warner, J.C. Arents, Pieter W. Postma, and Gary R. Jacobson. 1996. "Isolation and Characterization of a Mutation that Alters the Substrate Specificity of the Escherichia coli Glucose Permease", Journal of Bacteriology 178: 940-942.

Gary R. Jacobson. 1994. "Modular Structure of the Enzymes II of Bacterial Phosphotransferase Systems", in Proceedings of the International Symposium on Cellular and Molecular Biology of Phosphate and Phosphorylated Compounds in Microorganisms (Woods Hole, MA, 12-17 September, 1993), American Society for Microbiology, Washington, D.C., pp. 175-181.

Qing-Ping Weng and Gary R. Jacobson. 1993. "Role of a Conserved Histidine Residue, His-195, in the Activities of the Escherichia coli Mannitol Permease", Biochemistry 32, 11211-11216.

Qing-Ping Weng, Jacqueline Elder and Gary R. Jacobson. 1992. "Site-Specific Mutagenesis of Residues in the Escherichia coli Mannitol Permease That Have Been Suggested to be Important For Its Transport, Phosphorylation, and Chemo-reception Functions", Journal of Biological Chemistry 267, 19529-19535.

Jonathan Reizer, Aiala Reizer, Milton H. Saier, Jr. and Gary R. Jacobson. 1992. "A Proposed Link Between Nitrogen and Carbon Metabolism Involving Protein Phosphorylation in Bacteria", Protein Science 1, 722-726.

Questions and comments are always welcome.
Copyright © 1996, The Trustees of Boston University
This document was last modified on October 7, 2003.