Fructosamine-3-kinase-related-protein phosphorylates glucitolamines on the C-4 hydroxyl: novel substrate specificity of an enigmatic enzyme.

Benjamin Szwergold, Yefim Manevich, Leo Payne, Kerry Loomes

Dartmouth Medical School, Remsen 311-314, HB 7515, Hanover, NH 03755, USA. szwergold@dartmouth.edu

Biochemical and biophysical research communications 2007 Oct 5

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Fructosamine-3-kinase (FN3K) phosphorylates fructosamines to fructosamine-3-phosphates. Recent data from FN3K-knockout mouse indicate that this phosphorylation results in deglycation of proteins modified by non-enzymatic glycation process. A homolog of FN3K, the FN3K-related-protein (FN3KRP) displays 65% amino acid sequence identity with FN3K and is highly conserved in evolution. However, FN3KRP does not phosphorylate substrates of FN3K such as fructoselysine and its physiological function remains unknown. We observed that human erythrocytes that contain both enzymes phosphorylate N-methylglucamine (meglumine) to two products. One of these is meglumine-3-phosphate (Meg3P), an activity consistent with the known substrate specificity of FN3K. Here, we identify the second product as meglumine-4-phosphate (Meg4P) and show that it is produced specifically by FN3KRP. While it is unlikely that meglumine is the physiological target of FN3KRP, this novel specificity, along with FN3KRPs known phosphorylation of some ketosamines on the C-3 hydroxyl may prove useful in identifying the physiological substrates of this kinase.

Citation

Benjamin Szwergold, Yefim Manevich, Leo Payne, Kerry Loomes. Fructosamine-3-kinase-related-protein phosphorylates glucitolamines on the C-4 hydroxyl: novel substrate specificity of an enigmatic enzyme. Biochemical and biophysical research communications. 2007 Oct 5;361(4):870-5