Fructosamine-3-kinase-related-protein phosphorylates glucitolamines on the C-4 hydroxyl: novel substrate specificity of an enigmatic enzyme.
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.
Dartmouth Medical School, Remsen 311-314, HB 7515, Hanover, NH 03755, USA. szwergold@dartmouth.edu
Benjamin
B
Szwergold
Yefim
Y
Manevich
Leo
L
Payne
Kerry
K
Loomes
D000606:Amino Sugars / Q000737:chemistry; D004912:Erythrocytes / Q000201:enzymology; D008536:Meglumine / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D013012:Sorbitol / Q000031:analogs & derivatives / Q000378:metabolism; D013379:Substrate Specificity
D000606:Amino Sugars; D013012:Sorbitol; D008536:Meglumine; C479999:FN3KRP protein, human; D017853:Phosphotransferases (Alcohol Group Acceptor); C414347:fructosamine-3-kinase