Chang Shan, Hu Jian-ping, Lin Pi-yuan, Jiao Xiong, Tian Xu-hong
College of Informatics, South China Agricultural University, Guangzhou, China.
Mol Biosyst. 2010 Dec;6(12):2430-8. doi: 10.1039/c005266c. Epub 2010 Sep 14.
The L-arginine (Arg)/agmatine (Agm) antiporter AdiC is a vital transport protein of the arginine-dependent extreme acid resistance system of enteric bacteria. Recently, both substrate-free and Arg-bound structures of AdiC were determined by X-ray crystallography. In this article, the two different proteins were investigated with three simple models. Gaussian network model provided the information of conformational changes. It is found that Arg binding induces structural rearrangement in the extracellular domain, and transmembrane helix 6 (TM6) has the most pronounced trend of conformational changes. The moving directions of fluctuation regions were further ascertained by using anisotropy elastic network model and cross-correlation analysis. Interestingly, the two substrate-binding sites hypothesis of AdiC was confirmed directly by molecular docking. Furthermore, the binding preferences of these two sites were explained from the aspects of electrostatic complementarity and geometric matching. These simple coarse-grained analyses can be used as a general and quick method for the mechanism studies of transport proteins.
L-精氨酸（Arg）/胍丁胺（Agm）反向转运蛋白AdiC是肠道细菌精氨酸依赖性极端酸抗性系统的一种重要转运蛋白。最近，通过X射线晶体学确定了AdiC的无底物结构和结合精氨酸的结构。在本文中，用三种简单模型对这两种不同的蛋白质进行了研究。高斯网络模型提供了构象变化信息。研究发现，精氨酸结合会诱导细胞外结构域的结构重排，且跨膜螺旋6（TM6）具有最明显的构象变化趋势。通过使用各向异性弹性网络模型和互相关分析进一步确定了波动区域的移动方向。有趣的是，通过分子对接直接证实了AdiC的两个底物结合位点假说。此外，从静电互补性和几何匹配方面解释了这两个位点的结合偏好。这些简单的粗粒度分析可作为研究转运蛋白机制的通用且快速的方法。
