title: Effect of homocysteine thiolactone on structure and aggregation propensity of bovine pancreatic insulin.
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.
authors.affiliation: Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Iran.
authors.forename: Shima
authors.initials: S
authors.lastname: Jalili
authors.forename: Reza
authors.initials: R
authors.lastname: Yousefi
authors.forename: Mohammad-Mehdi
authors.initials: MM
authors.lastname: Papari
authors.forename: Ali Akbar
authors.initials: AA
authors.lastname: Moosavi-Movahedi
mesh_terms: D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D007328:Insulin / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008027:Light; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D011487:Protein Conformation / Q000187:drug effects; D055550:Protein Stability / Q000187:drug effects; D012542:Scattering, Radiation; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet
chemical_list: D007328:Insulin; D006710:Homocysteine; C007957:homocysteine thiolactone