Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Iran.
Protein J. 2011 Jun;30(5):299-307. doi: 10.1007/s10930-011-9333-1.
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.
同型半胱氨酸硫内酯（HCTL）是同型半胱氨酸的环状硫酯，对蛋白质的赖氨酸残基表现出很高的反应性。在本研究中，使用不同的光谱技术研究了在增加的 HCTL（0-500μM）浓度存在下，牛胰腺胰岛素的结构特性和聚集倾向。如本研究所示，HCTL 以剂量依赖的方式诱导胰岛素的明显结构改变和随后的聚集。HCTL 诱导胰岛素聚集也是一个顺序过程，其中富含α-螺旋结构的天然蛋白质逐渐转变为具有大量β-折叠的部分折叠构象。由于胰岛素 C 端 B 链在该蛋白质的稳定性中起关键作用，因此 HCTL 引起的结构改变/聚集可能是其 B 链上唯一赖氨酸残基（Lys29）的同型半胱氨酸化的结果。这项研究可能对 HCTL 对胰岛素结构的影响具有重要意义，特别是在与高同型半胱氨酸血症相关的病理状态下。
