Characterization of fructosamine 3-kinase related protein

Collard, François
(2004)

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Authors
  • Collard, FrançoisUCLouvain
    author
Supervisors
Larondelle, Yvan
 ;
Van Schaftingen, Emile
Abstract
The purpose of this thesis was to identify the biochemical function of fructosamine 3-kinase-related protein, a protein sharing about 65 % sequence identity with fructosamine 3-kinase (FN3K). Fructosamines are produced by a spontaneous reaction of glucose with amines, most particularly those of proteins. Phosphorylation of fructosamines on their third carbon results in their destabilization and in their removal from proteins. FN3K is therefore a protein repair enzyme. The Introduction is devoted to a short review on the best known protein repair enzymes. These are isoaspartyl-methyl transferase, methionyl-sulfoxide reductases, and fructosamine 3-kinase. The Results section comprises two articles. The first reports the sequence of FN3K-RP, its chromosomal localization, next to the FN3K gene, and the tissular distribution of its mRNA. Human recombinant FN3K-RP was produced. Unlike FN3K, FN3K-RP did not phosphorylate fructosamines, but ketosamines (both low-molecular-weight and protein-bound) with a D-configuration on carbon 3 (psicosamines and ribulosamines). FN3K was found to phosphorylate the three kinds of osamines. The second article demonstrates that FN3K-RP could also participate in protein deglycation. It is shown that FN3K-RP is active in erythrocytes. Furthermore, DMP can enter erythrocytes where it is phosphorylated to DMP 3-phosphate, indicating that it can be used as a competitive inhibitor of FN3K-RP. We also show that DMP increases the rate of accumulation of protein-bound osamines in erythrocytes incubated with elevated concentrations of ribose (precursor for ribulosamines) or allose (precursor for psicosamines) but not of glucose. These and other data indicate that FN3K-RP could participate in the removal of ribulosamines and psicosamines from proteins. The Discussion addresses several intriguing questions, most particularly the origin of FN3K-RP substrates under physiological conditions and the evolution of the enzymes belonging to the FN3K family.
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Collard, F. (2004). Characterization of fructosamine 3-kinase related protein. https://hdl.handle.net/2078.5/97513