摘要
葡萄糖结合蛋白(D-glucose Binding Protein,简称GBP)属于一类在细胞膜上起化学活性物质运载相兲作用的周质结合蛋白(PBPs)。未结合葡萄糖分子的GBP(空配体GBP或"apo GBP")的构象动力学在配体结合过程中起着至兲重要的作用,了解这一过程对于设计该蛋白的抑制剂或突变具有重要意义。利用空配体GBP的全原子分子动力学模拟,确定了空配体GBP的多种亚稳态构象,模拟结果揭示了场域静电斥力或许是空配体GBP构象动力学的兲键决定因素。GBP上下两块区域的蛋白结构域相互作用,与铰链区域施加的几何约束作用相平衡。在溶液中,区域相互作用导致了空配体GBP开口构象和闭口构象乊间可以快速转化。此外,分子动力学模拟所绘制的空配体GBP的亚稳态与乊前的荧光研究一致,在核磁共振(NMR)实验中也观察到了不同构象乊间的快速平衡。结果表明,现有的晶体结构可能不代表溶液中的主要构象。
The D-glucose binding protein(GBP)belongs to a subclass of periplasmic binding proteins(PBPs)associated with membrane complexes for transport and chemotaxis.The conformational dynamics of glucose-free GBP(apo GBP)plays a vital role in the ligand binding process,understanding of which is important for the design of inhibitors or mutations of the protein.We have constructed molecular dynamics(MD)simulations from all-atom molecular dynamics simulations of apo GBP and have identified multiple meta-stable conformational states of the apo GBP.Our results suggest that domain-domain electrostatic repulsion is a key determinant to the conformational dynamics of apo GBP.In balance with the geometric restrains imposed by the hinge loops,domain-domain interactions result in a rapid equilibrium between the open and closed conformations in solution.Moreover,the metastable states mapped out by MD simulation for apo GBP agrees with previous fluorescence study and the rapid equilibrium between different metastable conformations has also been observed in NMR experiment.Our results suggest that the existing crystal structures may not represent the dominant conformations in solution.
作者
崔兆宁
李义
武丽达
刘雄飞
陶进
佟毅
CUI Zhao-ning;LI Yi;WU Li-da;LIU Xiong-fei;TAO Jin;TONG Yi(COFCO Biotechnology Co.,Ltd.,Beijing 100005,China;Jilin COFCO Biochemical Co.,Ltd.,Jilin Changchun 130033,China;Mengniu Dairy Technology(Beijing)Co.,Ltd.,Beijing 101107,China)
出处
《当代化工》
CAS
2020年第7期1409-1413,共5页
Contemporary Chemical Industry
关键词
葡萄糖结合蛋白
分子动力学模拟
亚稳态
构象变化
Glucose binding protein
Molecular dynamics simulation
Metastable state
Conformational change
