Binding of vanadium compounds perturbs conformation and aggregation state of insulin  

作　　者：YANG Xiaogai, YANG Xiaoda, LI Rongchang and WANG Kui(Division of Bioinorganic Chemistry, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China National Research Laboratories of Natural and Biomimetic Drugs, Peking University, Beijing 100083, China) 

出　　处：《Progress in Natural Science:Materials International》2003年第1期39-45,共7页自然科学进展·国际材料（英文版）

基　　金：Supported by the National Natural Science Foundation of China (Grant No. 20101001)

摘　　要：The interactions between zinc-free insulin and vanadium compounds, NaVOs, VO(acac)2 and VO(ma)2?have been investigated by fluorescence spectroscopy, circular dichroism (CD) and Fourier-transformed infrared (FT-IR) spectroscopy. The results showed that binding of vanadium compounds produced a static quenching of the intrinsic fluorescence of insulin. The apparent association constants were determined to be (0.17 + 0.01) × 104 L·mol-1 for NaVO3, (2.8 ± 0.2) ×104 L·mol-1 for VO(acac)2, and (4.0 ± 0.1) ×10 L·mol for VO(ma)2, respectively. The light scattering intensity of insulin decreased upon incubation with the vanadium compounds, suggesting the disaggregation of insulin. The attenuation of the band at 273 nm of insulin CD spectra also supported the disaggre-gation of insulin observed above. A new band at 1650 - 1653 cm-1 appeared in the FT-IR spectra of insulin upon incubation with the vanadium compounds, indicating the formation of an a-helix structure at B (9-19) motif. This a-helix structure suggests a structural change of insulin from an extended conformation (T state) to a helical conformation (R state), which is essential for binding of insulin to its receptor. In conclusion, binding of vanadium compounds results in conformational changes and disaggregation of insulin. These changes might account for the enhancement of binding affinity for insulin to its receptor in the presence of vanadium compounds.The interactions between zinc-free insulin and vanadium compounds, NaVO3, VO(acac)2 and VO(ma)2, have been investigated by fluorescence spectroscopy, circular dichroism (CD) and Fourier-transformed infrared (FT-IR) spectroscopy. The results showed that binding of vanadium compounds produced a static quenching of the intrinsic fluorescence of insulin. The apparent association constants were determined to be (0.17±0.01)×104 L*mol-1 for NaVO3, (2.8±0.2)×104 L*mol-1 for VO(acac)2, and (4.0±0.1)×104 L*mol-1 for VO(ma)2, respectively. The light scattering intensity of insulin decreased upon incubation with the vanadium compounds, suggesting the disaggregation of insulin. The attenuation of the band at 273 nm of insulin CD spectra also supported the disaggregation of insulin observed above. A new band at 1650～1653 cm-1 appeared in the FT-IR spectra of insulin upon incubation with the vanadium compounds, indicating the formation of an α-helix structure at B (9-19) motif. This α-helix structure suggests a structural change of insulin from an extended conformation (T state) to a helical conformation (R state), which is essential for binding of insulin to its receptor. In conclusion, binding of vanadium compounds results in conformational changes and disaggregation of insulin. These changes might account for the enhancement of binding affinity for insulin to its receptor in the presence of vanadium compounds.

关 键 词：INSULIN vanadium compounds conformation. 

分 类 号：O657.3[理学—分析化学]