Howard, M.J. and Smales, C.M. (2005) NMR analysis of synthetic human serum albumin alpha-helix 28 identifies structural distortion upon amadori modification. Journal of Biological Chemistry, 280 (24). pp. 22582-22589. ISSN 0021-9258.
The non-enzymatic reaction between reducing sugars and long-lived proteins in vivo results in the formation of glycation and advanced glycation end products, which alter the properties of proteins including charge, helicity, and their tendency to aggregate. Such protein modifications are linked with various pathologies associated with the general aging process such as Alzheimer disease and the long-term complications of diabetes. Although it has been suggested that glycation and advanced glycation end products altered protein structure and helicity, little structural data and information currently exist on whether or not glycation does indeed influence or change local protein secondary structure. We have addressed this problem using a model helical peptide system containing a di-lysine motif derived from human serum albumin. We have shown that, in the presence of 50 mM glucose and at 37 degrees C, one of the lysine residues in the di-lysine motif within this peptide is preferentially glycated. Using NMR analysis, we have confirmed that the synthetic peptide constituting this helix does indeed form a alpha-helix in solution in the presence of 30% trifluoroethanol. Glycation of the model peptide resulted in the distortion of the alpha-helix, forcing the region of the helix around the site of glycation to adopt a 3(10) helical structure. This is the first reported evidence that glycation can influence or change local protein secondary structure. The implications and biological significance of such structural changes on protein function are discussed.
|Additional information:||934XB Times Cited:5 Cited References Count:37|
|Uncontrolled keywords:||protein modification advanced glycation nonenzymatic glycation empirical parameters folding problem glucose mobility model peptides fructose|
|Subjects:||Q Science > QD Chemistry
Q Science > QH Natural history > QH301 Biology
|Divisions:||Faculties > Science Technology and Medical Studies > School of Biosciences > Protein Science Group|
|Depositing User:||Mark Howard|
|Date Deposited:||16 Aug 2011 04:01|
|Last Modified:||05 Sep 2011 23:43|
|Resource URI:||http://kar.kent.ac.uk/id/eprint/5351 (The current URI for this page, for reference purposes)|
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