20201221 Wang AH Epub

Crystal structure of the N-terminal domain of TagH reveals a potential drug targeting site

Crystal structure of the N-terminal domain of TagH reveals a potential drug targeting site

Biochem Biophys Res Commun. 2021 Jan 15; 536:1-6. Epub 2020 Dec 22.
doi: 10.1016/j.bbrc.2020.12.028

閱讀文章

Yang CS, Huang WC, Ko TP, Wang YC, Wang AH, Chen Y.

摘要

Bacterial wall teichoic acids (WTAs) are synthesized intracellularly and exported by a two-component transporter, TagGH, comprising the transmembrane and ATPase subunits TagG and TagH. Here the dimeric structure of the N-terminal domain of TagH (TagH-N) was solved by single-wavelength anomalous diffraction using a selenomethionine-containing crystal, which shows an ATP-binding cassette (ABC) architecture with RecA-like and helical subdomains. Besides significant structural differences from other ABC transporters, a prominent patch of positively charged surface is seen in the center of the TagH-N dimer, suggesting a potential binding site for the glycerol phosphate chain of WTA. The ATPase activity of TagH-N was inhibited by clodronate, a bisphosphonate, in a non-competitive manner, consistent with the proposed WTA-binding site for drug targeting.