运输机
化学
分子动力学
草酸盐
膜转运蛋白
构象变化
反转运蛋白
生物物理学
结晶学
立体化学
生物化学
生物
膜
计算化学
基因
有机化学
作者
Jun Ohnuki,Titouan Jaunet-Lahary,Atsuko Yamashita,Kei-ichi Okazaki
标识
DOI:10.1021/acs.jpclett.3c03052
摘要
Transporter proteins change their conformations to carry their substrate across the cell membrane. The conformational dynamics is vital to understanding the transport function. We have studied the oxalate transporter (OxlT), an oxalate:formate antiporter from Oxalobacter formigenes, significant in avoiding kidney stone formation. The atomic structure of OxlT has been recently solved in the outward-open and occluded states. However, the inward-open conformation is still missing, hindering a complete understanding of the transporter. Here, we performed a Gaussian accelerated molecular dynamics simulation to sample the extensive conformational space of OxlT and successfully predicted the inward-open conformation where cytoplasmic substrate formate binding was preferred over oxalate binding. We also identified critical interactions for the inward-open conformation. The results were complemented by an AlphaFold2 structure prediction. Although AlphaFold2 solely predicted OxlT in the outward-open conformation, mutation of the identified critical residues made it partly predict the inward-open conformation, identifying possible state-shifting mutations.
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