You Yong, Liu Fang, Du Ke-Jie, Wen Ge-Bo, Lin Ying-Wu
Institute of Cardiovascular Disease & Key Lab for Arteriosclerology of Human Province, University of South China, Hengyang, 421001, China.
J Mol Model. 2014 Jul;20(7):2358. doi: 10.1007/s00894-014-2358-6. Epub 2014 Jul 3.
The interaction of blood glucose with heme proteins plays a key role in inducing diabetes, a serious disease threatening human health. In this study, we investigated the non-covalent interaction between glucose and myoglobin (Mb), both theoretically and experimentally, using molecular dynamics (MD) simulation combined with spectroscopic studies. It revealed that glucoses can occupy the side pocket of Mb, and bind closely to one of the xenon cavities in Mb, by hydrogen bonding interactions with two propionate groups of heme as well as surrounding amino acids. These interactions alter the conformation of the heme active site slightly and lead to an enhanced peroxidase activity of Mb, as determined by kinetic studies. This study provides general information for glucose-heme proteins interactions, and also for blood glucose-protein interactions for patients with diabetes.
血糖与血红素蛋白的相互作用在引发糖尿病（一种威胁人类健康的严重疾病）过程中起着关键作用。在本研究中，我们结合光谱研究，通过分子动力学（MD）模拟从理论和实验两方面研究了葡萄糖与肌红蛋白（Mb）之间的非共价相互作用。结果表明，葡萄糖可占据Mb的侧袋，并通过与血红素的两个丙酸基团以及周围氨基酸形成氢键相互作用，紧密结合于Mb中的一个氙腔。动力学研究表明，这些相互作用会轻微改变血红素活性位点的构象，并导致Mb的过氧化物酶活性增强。本研究为葡萄糖 - 血红素蛋白相互作用以及糖尿病患者的血糖 - 蛋白质相互作用提供了一般性信息。
