Effect of Homocysteine Thiolactone on Structure and Aggregation Propensity of Bovine Pancreatic Insulin |
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Authors: | Shima?Jalili Email author" target="_blank">Reza?YousefiEmail author Mohammad-Mehdi?Papari Ali?Akbar?Moosavi-Movahedi |
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Institution: | (1) Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran;(2) Department of Chemistry, Shiraz University of Technology, Shiraz, Iran;(3) Institute of Biochemistry and Biophysics (IBB), The University of Tehran, Tehran, Iran; |
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Abstract: | Homocysteine thiolactone (HCTL) is a cyclic thioester of homocysteine, showing high reactivity toward lysine residues of proteins.
In the present study the structural properties and aggregation propensity of bovine pancreatic insulin were studied in the
presences of increasing concentration of HCTL (0–500 μM), using different spectroscopic techniques. As shown in this study,
HCTL induces gross structural alterations and subsequently aggregation of insulin in a dose dependent manner. Also induction
of insulin aggregation by HCTL occurs in a sequential process, where native protein with alpha-helical abundant structure
gradually transforms into partially folded conformations with the significant amount of beta-sheet. Since C-terminal B-chain
of insulin plays a critical role in stability of this protein, the structural alteration/aggregation induced by HCTL can be
consequence of homocysteinylation of the only Lysine residue (Lys29) on its B-chain. This study may have important implications
regarding the effect of HCTL on structure of insulin particularly in the pathological states linked to hyperhomocysteinemia. |
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