Methylglyoxal-induced glycation affects protein topography

被引：24

作者：

Seidler, NW ^{[1
]}

Kowalewski, C ^{[1
]}

机构：

[1] Univ Hlth Sci, Dept Biochem, Kansas City, MO 64106 USA

来源：

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2003年 / 410卷 / 01期

关键词：

methylglyoxal; aspartate aminotransferase; intrinsic fluorescence; glycation;

D O I：

10.1016/S0003-9861(02)00662-8

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 [生物化学与分子生物学]; 081704 [应用化学];

摘要：

Methylglyoxal is a metabolic byproduct that is elevated in diabetic tissue. We examined the effects of methylglyoxal on cytosolic aspartate aminotransferase (cAAT), which is an enzyme previously shown to be modified by glyceraldehyde, acrolein, and ribose 5-phosphate. In the present study we observed that methylglyoxal caused real-time changes in tryptophan (intrinsic) fluorescence. Millimolar concentrations of methylglyoxal predominately decreased the fluorescence emission at 388 nm. While micromolar concentrations also decreased emission at 388 nm, low levels of methylglyoxal caused a prominent redshift in the wavelength of maximal emission. The changes in intrinsic fluorescence reflect definable changes in protein topography. These observations are consistent with a change in conformation that is more compact than that of native cAAT, suggesting that intramolecular cross-links (i.e., lysine-lysine) or hydrophobic pockets (i.e., carboxyethyl-lysines) were formed. Methylglyoxal also inhibited activity, and the inhibition correlated with the methylglyoxal-induced change in protein conformation. (C) 2002 Elsevier Science (USA). All rights reserved.

引用

页码：149 / 154

页数：6

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