@article{e3031e0dd2f0420b855c92a0a063529d,
title = "Crystal structure of the N-terminal domain of TagH reveals a potential drug targeting site",
abstract = "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.",
keywords = "ABC transporter, Bisphosphonates, Drug discovery, Wall teichoic acids",
author = "Yang, {Chia Shin} and Huang, {Wei Chien} and Ko, {Tzu Ping} and Wang, {Yu Chuan} and Wang, {Andrew H.J.} and Yeh Chen",
note = "Funding Information: The authors are grateful to NSRRC for beam time allocations and assistance with data collection. We also thank Professor Eric Oldfield at the University of Illinois, Urbana-Champaign, for generously providing bisphosphonate samples. This work was supported by grants from the Ministry of Science and Technology in Taiwan (108-2311-B241-001 and 109-2311-B241-001), China Medical University in Taiwan ( CMU109-MF-18 and CMU109-S-07 ), and Academia Sinica in Taiwan (AS-KPQ-106-TSPA and AS-KPQ-109-TPP2). Funding Information: The authors are grateful to NSRRC for beam time allocations and assistance with data collection. We also thank Professor Eric Oldfield at the University of Illinois, Urbana-Champaign, for generously providing bisphosphonate samples. This work was supported by grants from the Ministry of Science and Technology in Taiwan (108-2311-B241-001 and 109-2311-B241-001), China Medical University in Taiwan (CMU109-MF-18 and CMU109-S-07), and Academia Sinica in Taiwan (AS-KPQ-106-TSPA and AS-KPQ-109-TPP2). Publisher Copyright: {\textcopyright} 2020",
year = "2021",
month = jan,
day = "15",
doi = "10.1016/j.bbrc.2020.12.028",
language = "English",
volume = "536",
pages = "1--6",
journal = "Biochemical and Biophysical Research Communications",
issn = "0006-291X",
publisher = "Elsevier B.V.",
}