@article{053ac17b88f64fbc8bb7fe080e50b705,
title = "Moenomycin Biosynthesis: Structure and Mechanism of Action of the Prenyltransferase MoeN5",
abstract = "The structure of MoeN5, a unique prenyltransferase involved in the biosynthesis of the antibiotic moenomycin, is reported. MoeN5 catalyzes the reaction of geranyl diphosphate (GPP) with the cis-farnesyl group in phosphoglycolipid 5 to form the (C25) moenocinyl-sidechain-containing lipid 7. GPP binds to an allylic site (S1) and aligns well with known S1 inhibitors. Alkyl glycosides, glycolipids, can bind to both S1 and a second site, S2. Long sidechains in S2 are {"}bent{"} and co-locate with the homoallylic substrate isopentenyl diphosphate in other prenyltransferases. These observations support a MoeN5 mechanism in which 5 binds to S2 with its C6-C11 group poised to attack C1 in GPP to form the moenocinyl sidechain, with the more distal regions of 5 aligning with the distal glucose in decyl maltoside. The results are of general interest because they provide the first structures of MoeN5 and a structural basis for its mechanism of action, results that will facilitate the design of new antibiotics.",
keywords = "biosynthesis, drug discovery, enzyme mechanisms, isoprenoids, protein structure",
author = "Lilan Zhang and Chen, {Chun Chi} and Ko, {Tzu Ping} and Huang, {Jian Wen} and Yingying Zheng and Weidong Liu and Iren Wang and Malwal, {Satish R.} and Xinxin Feng and Ke Wang and Huang, {Chun Hsiang} and Hsu, {Shang Te Danny} and Wang, {Andrew H.J.} and Eric Oldfield and Guo, {Rey Ting}",
note = "Funding Information: Acknowledgements: This work was supported by the National Natural Science Foundation of China (grants 31200053, 31300615, 31400678 and 31470240), the Chinese Academy of Sciences (grant SZD-EW-Z-015-2), the United States Public Health Service (NIH grants CA158191 and GM065307), a Harriet A. Harlin Professorship and the University of Illinois Foundation/ Oldfield Research Fund. We thank the National Synchrotron Radiation Research Center of Taiwan for beam-time allocation and assistance with data collection. Publisher Copyright: {\textcopyright} 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.",
year = "2016",
month = apr,
day = "4",
doi = "10.1002/anie.201511388",
language = "English",
volume = "55",
pages = "4716--4720",
journal = "Angewandte Chemie - International Edition",
issn = "1433-7851",
publisher = "John Wiley and Sons Ltd",
number = "15",
}