This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Polyamines, including putrescine, spermidine, and spermine, are essential for normal cell growth in both prokaryotic and eukaryotic cells. We are interested in studying a number of enzymes involved in polyamine biosynthesis and degradation. These enzymes include S-adenosylmethionine decarboxylase (AdoMetDC), the AdoMetDC prozyme, spermine oxidase, and the fusion protein of AdoMetDC/SpdSyn. AdoMetDC catalyzes the decarboxylation of S-adenosylmethionine (AdoMet) to form S-adenosylmethioninamine (dcAdoMet). Previously, the Ealick laboratory has solved the structure of Thermotoga maritima, human, and potato AdoMetDC. The catalytic activity of AdoMetDC from Trypanosoma brucei (T. brucei), Trypanosoma cruzi (T. cruzi), Leishmania major (L. major), and Leishmania braziliensis (L. braziliensis) is enhanced by the formation of a heterodimer with a catalytically inactive regulatory subunit, termed the prozyme. Spermine oxidase is an inducible enzyme that is part of the polyamine degradation pathway;it breaks down spermine directly to spermidine, skipping the rate limiting addition of an acetyl group to spermine that other polyamine degradation enzymes require. This makes it much more efficient in the removal of spermine from cells, as well as producing high levels of the reaction byproduct hydrogen peroxide, which is cytotoxic to cancer cells. In Tetrahymena thermophila, AdoMetDC is coupled with spermidine synthase (SpdSyn), which transfers the propylamine group from decarboxylated SAM to putrescine to generate methythioadenosine and spermidine, as a bifunctional enzyme.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Biotechnology Resource Grants (P41)
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Cornell University
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