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Diabetes 52:2888-2895, 2003
© 2003 by the American Diabetes Association, Inc.

A Mammalian Protein Homologous to Fructosamine-3-Kinase Is a Ketosamine-3-Kinase Acting on Psicosamines and Ribulosamines but not on Fructosamines

François Collard1, Ghislain Delpierre1, Vincent Stroobant2, Gert Matthijs3, and Emile Van Schaftingen1

1 Laboratory of Physiological Chemistry, ICP, and Université Catholique de Louvain, Brussels, Belgium
2 Brussels Branch of the Ludwig Institute, Brussels, Belgium
3 Center for Human Genetics, University of Leuven, Leuven, Belgium

Fructosamine-3-kinase (FN3K) is an enzyme that appears to be responsible for the removal of fructosamines from proteins. In this study, we report the sequence of human and mouse cDNAs encoding proteins sharing 65% sequence identity with FN3K. The genes encoding FN3K and FN3K-related protein (FN3K-RP) are present next to each other on human chromosome 17q25, and they both have a similar 6-exon structure. Northern blots of mouse tissues RNAs indicate a high level of expression of both genes in bone marrow, brain, kidneys, and spleen. Human FN3K-RP was transfected in human embryonic kidney (HEK) cells, and the expressed protein was partially purified by chromatography on Blue Sepharose. Unlike FN3K, FN3K-RP did not phosphorylate fructoselysine, 1-deoxy-1-morpholino-fructose, or lysozyme glycated with glucose. In a more systematic screening for potential substrates for FN3K-RP, we found, however, that both enzymes phosphorylated ketosamines with a D-configuration in C3 (psicoselysine, 1-deoxy-1-morpholino-psicose, 1-deoxy-1-morpholino-ribulose, lysozyme glycated with allose—the C3 epimer of glucose, or with ribose). Tandem mass spectrometry and nuclear magnetic resonance analysis of the product of phosphorylation of 1-deoxy-1-morpholino-psicose by FN3K-RP indicated that this enzyme phosphorylates the third carbon of the sugar moiety. These results indicate that FN3K-RP is a ketosamine-3-kinase (ketosamine-3-kinase 2). This enzyme presumably plays a role in freeing proteins from ribulosamines or psicosamines, which might arise in a several step process, from the reaction of amines with glucose and/or glycolytic intermediates. This role is shared by fructosamine-3-kinase (ketosamine-3-kinase 1), which has, in addition, the unique capacity to phosphorylate fructosamines.


Address correspondence and reprint requests to E. Van Schaftingen, Avenue Hippocrate 75, B-1200, Brussels, Belgium. E-mail: vanschaftingen{at}bchm.ucl.ac.be


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J. Biol. Chem.Home page
J. Delplanque, G. Delpierre, F. R. Opperdoes, and E. Van Schaftingen
Tissue Distribution and Evolution of Fructosamine 3-Kinase and Fructosamine 3-Kinase-related Protein
J. Biol. Chem., November 5, 2004; 279(45): 46606 - 46613.
[Abstract] [Full Text] [PDF]




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Copyright © 2003 by the American Diabetes Association.