Fructosamine-3-kinase-related-protein phosphorylates glucitolamines on the C-4 hydroxyl: novel substrate specificity of an enigmatic enzyme.
Fructosamine-3-kinase-related-protein phosphorylates glucitolamines on the C-4 hydroxyl: novel substrate specificity of an enigmatic enzyme.
复制标题
果糖胺-3-激酶相关蛋白在 C-4 羟基上磷酸化葡萄糖醇胺：一种神秘酶的新型底物特异性。
DOI：
10.1016/j.bbrc.2007.07.127
复制
发表时间：
2007
影响因子：
3.1
通讯作者：
Loomes,Kerry
中科院分区：
文献类型：
--
作者：
Szwergold,Benjamin;Manevich,Yefim;Payne,Leo;Loomes,Kerry
果糖胺-3-激酶 (FN3K) 将果糖胺磷酸化为果糖胺-3-磷酸。来自 FN3K 敲除小鼠的最新数据表明，这种磷酸化导致非酶糖化过程修饰的蛋白质去糖化。 FN3K 相关蛋白 (FN3KRP) 是 FN3K 的同源物，与 FN3K 具有 65% 的氨基酸序列同一性，并且在进化中高度保守。然而，FN3KRP 不会磷酸化 FN3K 的底物（如果糖赖氨酸），其生理功能仍不清楚。我们观察到含有这两种酶的人类红细胞将 N-甲基葡糖胺（葡甲胺）磷酸化为两种产物。其中之一是 3-磷酸葡甲胺 (Meg3P)，其活性与 FN3K 已知的底物特异性一致。在这里，我们将第二种产物鉴定为 4-磷酸葡甲胺 (Meg4P)，并表明它是由 FN3KRP 专门产生的。虽然葡甲胺不太可能是 FN3KRP 的生理靶标，但这种新颖的特异性以及 FN3KRP 已知的 C-3 羟基上某些酮胺的磷酸化可能有助于识别该激酶的生理底物。
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.