Cryo-electron Microscopy Structure and Transport Mechanism of a Wall Teichoic Acid ABC Transporter
Li Chen, Wen‐Tao Hou, Tao Fan, Banghui Liu, Ting Pan, Yuhui Li, Yong‐Liang Jiang, Wen Wen, Zhipeng Chen, Linfeng Sun, Cong‐Zhao Zhou, Yuxing Chen
Abstract
(MRSA). The ABC transporter TarGH is indispensable for flipping WTA precursor from cytoplasm to the extracellular space, thus making it a promising drug target for anti-MRSA agents. The 3.9-Å cryo-EM structure of a TarGH homolog helps us to decode the binding site and inhibitory mechanism of a recently reported inhibitor, Targocil, and provides a structural platform for rational design and optimization of potential antibiotics. Moreover, we propose a "crankshaft conrod" mechanism to explain how a big substrate is translocated through subtle conformational changes of type II exporters. These findings advance our understanding of anti-MRSA drug design and ABC transporters.