Herbert M. Kagan
Professor of Biochemistry
Department of Biochemistry
Boston University School of Medicine
Silvio Conte Building, K304
72 E. Concord Street
Boston, MA 02118
Phone:617- 638-4064
Fax: 617-638-5339
Email: kagan@biochem.bumc.bu.edu
Education
B.A., M.A., University of Massachusetts, MA
Ph.D., Tufts University, MA
Research Interest
Enzymology and biology of amine oxidases
The oxidative deamination of primary amines by copper-dependent amine oxidases are reactions which are important for homeostasis, growth and repair. Particular effort is addressed toward lysyl oxidase which oxidizes peptidyl lysine in elastin and collagen and thus initiates inter-peptide covalent crosslinkage formation essential to the extracellular deposition of insoluble fibers of these proteins in connective tissues. Surprisingly, we have observed extracellular lysyl oxidase entering vascular smooth muscle cells followed by its rapid translocation into the cell nucleus. We have also identified the presence of lysyl oxidase in the nuclei of fibrogenic fibroblast cells. While we have made considerable progress in the elucidation of the catalytic mechanism and nature of the substrate specificity of this enzyme, current efforts are directed at analysis of the mechanism by which the enzyme enters the cell and its nucleus as well as the exploration of possible intracellular substrates and phenotypic cellular responses to intracellular and intranuclear lysyl oxidase. Additional efforts are directed at the application of site-directed mutagenesis to analyze key structure-function relationships of this catalyst.
Representative Publications
Lucero, H. A., and Kagan, H. M. (2006) Lysyl oxidase: an oxidative enzyme and effector of cell function. Cell Mol Life Sci. 63, 2304-2316.
Jones, M.R., Zhao, Z, Sullivan, C.P., Schrieber, B.M., Stone, P., Cohen, R.A., Kagan, H.M., and Ravid, K. (2004) A3 adenosine receptor deficiency does not influence atherogenesis. J. Cell Biochem. 92, 1034-1043.
Jeay, S., S. Pianetti, H.M. Kagan, and G.E. Sonenshein. (2003) Lysyl oxidase inhibits Ras mediated transformation by preventing activation of NF-?B. Mol. Cell Biol. 23, 2251-2263.
Gilad G.M., Kagan H. M., and Gilad V.H. (2005) Evidence for increased lysyl oxidase, the extracellular matrix-forming enzyme, in Alzheimer’s disease brain. Neurosci Lett. 376, 210-214.
Liu, G., Nellaiappan, K., and Kagan, H.M. (1997) Irreversible inhibition of lysyl oxidase by homocysteine thiolactone and its selenium and oxygen analogues. Implications for homocystinuria. J. Biol. Chem. 272, 32370-32377.
Li, W., Nellaiappan, K., Strassmaier, T., Graham, L., Thomas, K. M., and Kagan, H. M. (1997) Localization and activity of lysyl oxidase within nuclei of fibrogenic cells. Proc. Natl. Acad. Sci.
